Ignet

Gene Information

Gene symbol: TBX21

Gene name: T-box 21

HGNC ID: 11599

Synonyms: TBLYM, T-bet

Related Genes

#	Gene Symbol	Number of hits
1	BCL6	1 hits
2	CCR6	1 hits
3	CD28	1 hits
4	CD4	1 hits
5	CD8A	1 hits
6	CD8B	1 hits
7	CXCL9	1 hits
8	CXCR3	1 hits
9	DNASE1	1 hits
10	EOMES	1 hits
11	ESR1	1 hits
12	FOXP3	1 hits
13	GATA3	1 hits
14	GZMB	1 hits
15	HLX	1 hits
16	ICOS	1 hits
17	IFNG	1 hits
18	IKZF1	1 hits
19	IL10	1 hits
20	IL12A	1 hits
21	IL12B	1 hits
22	IL12RB2	1 hits
23	IL17A	1 hits
24	IL18	1 hits
25	IL18RAP	1 hits
26	IL1B	1 hits
27	IL4	1 hits
28	IRF1	1 hits
29	IRF8	1 hits
30	JAK3	1 hits
31	JMJD3	1 hits
32	MAPK1	1 hits
33	MYD88	1 hits
34	RORC	1 hits
35	RUNX3	1 hits
36	SETD7	1 hits
37	SIN3A	1 hits
38	SOCS1	1 hits
39	SOCS3	1 hits
40	SOCS6	1 hits
41	STAT1	1 hits
42	STAT4	1 hits
43	T	1 hits
44	TBX19	1 hits
45	TCF7	1 hits
46	TGFB1	1 hits
47	TGFBR1	1 hits
48	TH1L	1 hits
49	TNF	1 hits
50	TNFRSF18	1 hits
51	TWIST1	1 hits

Related Sentences

#	PMID	Sentence
1	12447360	We found that in these conditions human naive T cells acquired stable histone hyperacetylation at either the Ifng or Il4 promoter.
2	12447360	Such cytokine flexibility was absent in a subset of T(H)2 cells that failed to up-regulate T-bet and to express interferon-gamma when stimulated under T(H)1 conditions.
3	15183000	This publication describes the cloning of full or partial length sequences for pig TBX21 (T-bet), MYD88, ICSBP1, CD8A (CD8alpha), CD8B (CD8beta), and CD28 cDNAs.
4	15183000	Real-time PCR assays have been developed for the relative quantitation of these products as well as previously characterized transcripts that encode exon A-containing CD45, HLX1, IRF1, STAT1 and RPL32.
5	15183000	When used for examining temporal immune gene expression in the liver of Toxoplasma gondii infected pigs, the positive regulators of Th1 responses, IRF1, MYD88, and STAT1, were found to be expressed prior to the simultaneous upregulation of interferon gamma (IFNG), HLX1 and TBX21 gene expression.
6	15183000	In contrast, in the mesenteric lymph node (MLN), only expression of IRF1 and IFNG was significantly upregulated.
7	15183000	This publication describes the cloning of full or partial length sequences for pig TBX21 (T-bet), MYD88, ICSBP1, CD8A (CD8alpha), CD8B (CD8beta), and CD28 cDNAs.
8	15183000	Real-time PCR assays have been developed for the relative quantitation of these products as well as previously characterized transcripts that encode exon A-containing CD45, HLX1, IRF1, STAT1 and RPL32.
9	15183000	When used for examining temporal immune gene expression in the liver of Toxoplasma gondii infected pigs, the positive regulators of Th1 responses, IRF1, MYD88, and STAT1, were found to be expressed prior to the simultaneous upregulation of interferon gamma (IFNG), HLX1 and TBX21 gene expression.
10	15183000	In contrast, in the mesenteric lymph node (MLN), only expression of IRF1 and IFNG was significantly upregulated.
11	15241679	Therefore, we focused on the Th1-specific T-box transcription factor gene (T-bet), which contributes to the induction of the hallmark Th1 cytokine, IFN-gamma.
12	15241679	Furthermore, Gln33 T-bet showed a significantly higher transcriptional activity of the IFNG gene via a dual luciferase reporter assay.
13	15241679	Our study suggests the first evidence of an association between type 1 diabetes and polymorphisms in the T-bet gene, and that variation in T-bet transcriptional activity may play a role in the development of type 1 diabetes, possibly through the effect on IFN-gamma production in Th1 cells.
14	15241679	Therefore, we focused on the Th1-specific T-box transcription factor gene (T-bet), which contributes to the induction of the hallmark Th1 cytokine, IFN-gamma.
15	15241679	Furthermore, Gln33 T-bet showed a significantly higher transcriptional activity of the IFNG gene via a dual luciferase reporter assay.
16	15241679	Our study suggests the first evidence of an association between type 1 diabetes and polymorphisms in the T-bet gene, and that variation in T-bet transcriptional activity may play a role in the development of type 1 diabetes, possibly through the effect on IFN-gamma production in Th1 cells.
17	15241679	Therefore, we focused on the Th1-specific T-box transcription factor gene (T-bet), which contributes to the induction of the hallmark Th1 cytokine, IFN-gamma.
18	15241679	Furthermore, Gln33 T-bet showed a significantly higher transcriptional activity of the IFNG gene via a dual luciferase reporter assay.
19	15241679	Our study suggests the first evidence of an association between type 1 diabetes and polymorphisms in the T-bet gene, and that variation in T-bet transcriptional activity may play a role in the development of type 1 diabetes, possibly through the effect on IFN-gamma production in Th1 cells.
20	15280353	To better understand the control of T helper (TH) 1-expressed genes, we compared and contrasted acetylation and expression for three key genes, IFNG, TBET, and IL18RAP and found them to be distinctly regulated.
21	15280353	The TBET and the IFNG genes, but not the IL18RAP gene, showed preferential acetylation of histones H3 and H4 during TH1 differentiation.
22	15280353	Histone H3 acetylation of IFNG and TBET genes occurred with different kinetics, however, and was distinctively regulated by cytokines.
23	15280353	Interleukin (IL)-12 and IL-18 enhanced the histone acetylation of the IFNG gene.
24	15280353	By contrast, histone acetylation of the TBET gene was markedly suppressed by IL-4, whereas IL-12 and IL-18 had only modest effects suggesting that histone acetylation during TH1 differentiation is a process that is regulated by various factors at multiple levels.
25	15280353	By treating Th2 cells with a histone deacetylase inhibitor, we restored histone acetylation of the IFNG and TBET genes, but it did not fully restore their expression in TH2 cells, again suggesting that histone acetylation explains one but not all the aspects of TH1-specific gene expression.
26	15280353	To better understand the control of T helper (TH) 1-expressed genes, we compared and contrasted acetylation and expression for three key genes, IFNG, TBET, and IL18RAP and found them to be distinctly regulated.
27	15280353	The TBET and the IFNG genes, but not the IL18RAP gene, showed preferential acetylation of histones H3 and H4 during TH1 differentiation.
28	15280353	Histone H3 acetylation of IFNG and TBET genes occurred with different kinetics, however, and was distinctively regulated by cytokines.
29	15280353	Interleukin (IL)-12 and IL-18 enhanced the histone acetylation of the IFNG gene.
30	15280353	By contrast, histone acetylation of the TBET gene was markedly suppressed by IL-4, whereas IL-12 and IL-18 had only modest effects suggesting that histone acetylation during TH1 differentiation is a process that is regulated by various factors at multiple levels.
31	15280353	By treating Th2 cells with a histone deacetylase inhibitor, we restored histone acetylation of the IFNG and TBET genes, but it did not fully restore their expression in TH2 cells, again suggesting that histone acetylation explains one but not all the aspects of TH1-specific gene expression.
32	15280353	To better understand the control of T helper (TH) 1-expressed genes, we compared and contrasted acetylation and expression for three key genes, IFNG, TBET, and IL18RAP and found them to be distinctly regulated.
33	15280353	The TBET and the IFNG genes, but not the IL18RAP gene, showed preferential acetylation of histones H3 and H4 during TH1 differentiation.
34	15280353	Histone H3 acetylation of IFNG and TBET genes occurred with different kinetics, however, and was distinctively regulated by cytokines.
35	15280353	Interleukin (IL)-12 and IL-18 enhanced the histone acetylation of the IFNG gene.
36	15280353	By contrast, histone acetylation of the TBET gene was markedly suppressed by IL-4, whereas IL-12 and IL-18 had only modest effects suggesting that histone acetylation during TH1 differentiation is a process that is regulated by various factors at multiple levels.
37	15280353	By treating Th2 cells with a histone deacetylase inhibitor, we restored histone acetylation of the IFNG and TBET genes, but it did not fully restore their expression in TH2 cells, again suggesting that histone acetylation explains one but not all the aspects of TH1-specific gene expression.
38	15280353	To better understand the control of T helper (TH) 1-expressed genes, we compared and contrasted acetylation and expression for three key genes, IFNG, TBET, and IL18RAP and found them to be distinctly regulated.
39	15280353	The TBET and the IFNG genes, but not the IL18RAP gene, showed preferential acetylation of histones H3 and H4 during TH1 differentiation.
40	15280353	Histone H3 acetylation of IFNG and TBET genes occurred with different kinetics, however, and was distinctively regulated by cytokines.
41	15280353	Interleukin (IL)-12 and IL-18 enhanced the histone acetylation of the IFNG gene.
42	15280353	By contrast, histone acetylation of the TBET gene was markedly suppressed by IL-4, whereas IL-12 and IL-18 had only modest effects suggesting that histone acetylation during TH1 differentiation is a process that is regulated by various factors at multiple levels.
43	15280353	By treating Th2 cells with a histone deacetylase inhibitor, we restored histone acetylation of the IFNG and TBET genes, but it did not fully restore their expression in TH2 cells, again suggesting that histone acetylation explains one but not all the aspects of TH1-specific gene expression.
44	15280353	To better understand the control of T helper (TH) 1-expressed genes, we compared and contrasted acetylation and expression for three key genes, IFNG, TBET, and IL18RAP and found them to be distinctly regulated.
45	15280353	The TBET and the IFNG genes, but not the IL18RAP gene, showed preferential acetylation of histones H3 and H4 during TH1 differentiation.
46	15280353	Histone H3 acetylation of IFNG and TBET genes occurred with different kinetics, however, and was distinctively regulated by cytokines.
47	15280353	Interleukin (IL)-12 and IL-18 enhanced the histone acetylation of the IFNG gene.
48	15280353	By contrast, histone acetylation of the TBET gene was markedly suppressed by IL-4, whereas IL-12 and IL-18 had only modest effects suggesting that histone acetylation during TH1 differentiation is a process that is regulated by various factors at multiple levels.
49	15280353	By treating Th2 cells with a histone deacetylase inhibitor, we restored histone acetylation of the IFNG and TBET genes, but it did not fully restore their expression in TH2 cells, again suggesting that histone acetylation explains one but not all the aspects of TH1-specific gene expression.
50	15304658	When linked to the murine Ifng gene (-3.4 to +5.6 kb) and transiently transfected into EL-4 cells, these elements clearly enhanced IFN-gamma expression in response to ionomycin and phorbol 12-myristate 13-acetate and weakly enhanced expression in response to T-bet.
51	15304658	A DNase I hypersensitive site and extragenic transcripts at IFNgCNS2 correlated positively with the capacity of primary T cell subsets to produce IFN-gamma.
52	15304658	Transcriptionally favorable histone modifications in the Ifng promoter, intronic regions, IFNgCNS2, and, although less pronounced, IFNgCNS1 increased as naïve T cells differentiated into IFN-gamma-producing effector CD8+ and T helper (TH) 1 T cells, but not into TH2 T cells.
53	15304658	Like IFN-gamma expression, these histone modifications were T-bet-dependent in CD4+ cells, but not CD8+ T cells.
54	15304658	When linked to the murine Ifng gene (-3.4 to +5.6 kb) and transiently transfected into EL-4 cells, these elements clearly enhanced IFN-gamma expression in response to ionomycin and phorbol 12-myristate 13-acetate and weakly enhanced expression in response to T-bet.
55	15304658	A DNase I hypersensitive site and extragenic transcripts at IFNgCNS2 correlated positively with the capacity of primary T cell subsets to produce IFN-gamma.
56	15304658	Transcriptionally favorable histone modifications in the Ifng promoter, intronic regions, IFNgCNS2, and, although less pronounced, IFNgCNS1 increased as naïve T cells differentiated into IFN-gamma-producing effector CD8+ and T helper (TH) 1 T cells, but not into TH2 T cells.
57	15304658	Like IFN-gamma expression, these histone modifications were T-bet-dependent in CD4+ cells, but not CD8+ T cells.
58	16237092	Using conditional introduction of dominant-negative factors, we now show that T-bet and GATA-3 are far more critical in establishment than maintenance of IFN-gamma and IL-4 activity during Th1 and Th2 maturation, respectively.
59	16237092	T-bet plus Hlx can disrupt ifng silencing when introduced into developing Th2 cells, but they fail to perturb ifng silencing in mature Th2 cells.
60	16237092	Using conditional introduction of dominant-negative factors, we now show that T-bet and GATA-3 are far more critical in establishment than maintenance of IFN-gamma and IL-4 activity during Th1 and Th2 maturation, respectively.
61	16237092	T-bet plus Hlx can disrupt ifng silencing when introduced into developing Th2 cells, but they fail to perturb ifng silencing in mature Th2 cells.
62	16286661	In T cells, long-range histone acetylation depended on stimulation that drives both T helper (Th) 1 differentiation and active transcription, and it depended completely or partially on the presence of Stat4 or T-bet, respectively, two transcription factors that are required for Th1 lineage commitment.
63	16520391	T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription.
64	16520391	T helper type 1 (Th1) development is facilitated by interrelated changes in key intracellular factors, particularly signal transducer and activator of transcription (STAT)4, T-bet, and GATA-3.
65	16520391	Here we show that CD4+ cells from T-bet-/- mice are skewed toward Th2 differentiation by high endogenous GATA-3 levels but exhibit virtually normal Th1 differentiation provided that GATA-3 levels are regulated at an early stage by anti-interleukin (IL)-4 blockade of IL-4 receptor (R) signaling.
66	16520391	In addition, under these conditions, Th1 cells from T-bet-/- mice manifest IFNG promotor accessibility as detected by histone acetylation and deoxyribonuclease I hypersensitivity.
67	16520391	In related studies, we show that the negative effect of GATA-3 on Th1 differentiation in T-bet-/- cells arises from its ability to suppress STAT4 levels, because if this is prevented by a STAT4-expressing retrovirus, normal Th1 differentiation is observed.
68	16520391	Finally, we show that retroviral T-bet expression in developing and established Th2 cells leads to down-regulation of GATA-3 levels.
69	16520391	These findings lead to a model of T cell differentiation that holds that naive T cells tend toward Th2 differentiation through induction of GATA-3 and subsequent down-regulation of STAT4/IL-12Rbeta2 chain unless GATA-3 levels or function is regulated by T-bet.
70	16520391	Thus, the principal function of T-bet in developing Th1 cells is to negatively regulate GATA-3 rather than to positively regulate the IFNG gene.
71	16520391	T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription.
72	16520391	T helper type 1 (Th1) development is facilitated by interrelated changes in key intracellular factors, particularly signal transducer and activator of transcription (STAT)4, T-bet, and GATA-3.
73	16520391	Here we show that CD4+ cells from T-bet-/- mice are skewed toward Th2 differentiation by high endogenous GATA-3 levels but exhibit virtually normal Th1 differentiation provided that GATA-3 levels are regulated at an early stage by anti-interleukin (IL)-4 blockade of IL-4 receptor (R) signaling.
74	16520391	In addition, under these conditions, Th1 cells from T-bet-/- mice manifest IFNG promotor accessibility as detected by histone acetylation and deoxyribonuclease I hypersensitivity.
75	16520391	In related studies, we show that the negative effect of GATA-3 on Th1 differentiation in T-bet-/- cells arises from its ability to suppress STAT4 levels, because if this is prevented by a STAT4-expressing retrovirus, normal Th1 differentiation is observed.
76	16520391	Finally, we show that retroviral T-bet expression in developing and established Th2 cells leads to down-regulation of GATA-3 levels.
77	16520391	These findings lead to a model of T cell differentiation that holds that naive T cells tend toward Th2 differentiation through induction of GATA-3 and subsequent down-regulation of STAT4/IL-12Rbeta2 chain unless GATA-3 levels or function is regulated by T-bet.
78	16520391	Thus, the principal function of T-bet in developing Th1 cells is to negatively regulate GATA-3 rather than to positively regulate the IFNG gene.
79	16520391	T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription.
80	16520391	T helper type 1 (Th1) development is facilitated by interrelated changes in key intracellular factors, particularly signal transducer and activator of transcription (STAT)4, T-bet, and GATA-3.
81	16520391	Here we show that CD4+ cells from T-bet-/- mice are skewed toward Th2 differentiation by high endogenous GATA-3 levels but exhibit virtually normal Th1 differentiation provided that GATA-3 levels are regulated at an early stage by anti-interleukin (IL)-4 blockade of IL-4 receptor (R) signaling.
82	16520391	In addition, under these conditions, Th1 cells from T-bet-/- mice manifest IFNG promotor accessibility as detected by histone acetylation and deoxyribonuclease I hypersensitivity.
83	16520391	In related studies, we show that the negative effect of GATA-3 on Th1 differentiation in T-bet-/- cells arises from its ability to suppress STAT4 levels, because if this is prevented by a STAT4-expressing retrovirus, normal Th1 differentiation is observed.
84	16520391	Finally, we show that retroviral T-bet expression in developing and established Th2 cells leads to down-regulation of GATA-3 levels.
85	16520391	These findings lead to a model of T cell differentiation that holds that naive T cells tend toward Th2 differentiation through induction of GATA-3 and subsequent down-regulation of STAT4/IL-12Rbeta2 chain unless GATA-3 levels or function is regulated by T-bet.
86	16520391	Thus, the principal function of T-bet in developing Th1 cells is to negatively regulate GATA-3 rather than to positively regulate the IFNG gene.
87	16520391	T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription.
88	16520391	T helper type 1 (Th1) development is facilitated by interrelated changes in key intracellular factors, particularly signal transducer and activator of transcription (STAT)4, T-bet, and GATA-3.
89	16520391	Here we show that CD4+ cells from T-bet-/- mice are skewed toward Th2 differentiation by high endogenous GATA-3 levels but exhibit virtually normal Th1 differentiation provided that GATA-3 levels are regulated at an early stage by anti-interleukin (IL)-4 blockade of IL-4 receptor (R) signaling.
90	16520391	In addition, under these conditions, Th1 cells from T-bet-/- mice manifest IFNG promotor accessibility as detected by histone acetylation and deoxyribonuclease I hypersensitivity.
91	16520391	In related studies, we show that the negative effect of GATA-3 on Th1 differentiation in T-bet-/- cells arises from its ability to suppress STAT4 levels, because if this is prevented by a STAT4-expressing retrovirus, normal Th1 differentiation is observed.
92	16520391	Finally, we show that retroviral T-bet expression in developing and established Th2 cells leads to down-regulation of GATA-3 levels.
93	16520391	These findings lead to a model of T cell differentiation that holds that naive T cells tend toward Th2 differentiation through induction of GATA-3 and subsequent down-regulation of STAT4/IL-12Rbeta2 chain unless GATA-3 levels or function is regulated by T-bet.
94	16520391	Thus, the principal function of T-bet in developing Th1 cells is to negatively regulate GATA-3 rather than to positively regulate the IFNG gene.
95	16520391	T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription.
96	16520391	T helper type 1 (Th1) development is facilitated by interrelated changes in key intracellular factors, particularly signal transducer and activator of transcription (STAT)4, T-bet, and GATA-3.
97	16520391	Here we show that CD4+ cells from T-bet-/- mice are skewed toward Th2 differentiation by high endogenous GATA-3 levels but exhibit virtually normal Th1 differentiation provided that GATA-3 levels are regulated at an early stage by anti-interleukin (IL)-4 blockade of IL-4 receptor (R) signaling.
98	16520391	In addition, under these conditions, Th1 cells from T-bet-/- mice manifest IFNG promotor accessibility as detected by histone acetylation and deoxyribonuclease I hypersensitivity.
99	16520391	In related studies, we show that the negative effect of GATA-3 on Th1 differentiation in T-bet-/- cells arises from its ability to suppress STAT4 levels, because if this is prevented by a STAT4-expressing retrovirus, normal Th1 differentiation is observed.
100	16520391	Finally, we show that retroviral T-bet expression in developing and established Th2 cells leads to down-regulation of GATA-3 levels.
101	16520391	These findings lead to a model of T cell differentiation that holds that naive T cells tend toward Th2 differentiation through induction of GATA-3 and subsequent down-regulation of STAT4/IL-12Rbeta2 chain unless GATA-3 levels or function is regulated by T-bet.
102	16520391	Thus, the principal function of T-bet in developing Th1 cells is to negatively regulate GATA-3 rather than to positively regulate the IFNG gene.
103	16520391	T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription.
104	16520391	T helper type 1 (Th1) development is facilitated by interrelated changes in key intracellular factors, particularly signal transducer and activator of transcription (STAT)4, T-bet, and GATA-3.
105	16520391	Here we show that CD4+ cells from T-bet-/- mice are skewed toward Th2 differentiation by high endogenous GATA-3 levels but exhibit virtually normal Th1 differentiation provided that GATA-3 levels are regulated at an early stage by anti-interleukin (IL)-4 blockade of IL-4 receptor (R) signaling.
106	16520391	In addition, under these conditions, Th1 cells from T-bet-/- mice manifest IFNG promotor accessibility as detected by histone acetylation and deoxyribonuclease I hypersensitivity.
107	16520391	In related studies, we show that the negative effect of GATA-3 on Th1 differentiation in T-bet-/- cells arises from its ability to suppress STAT4 levels, because if this is prevented by a STAT4-expressing retrovirus, normal Th1 differentiation is observed.
108	16520391	Finally, we show that retroviral T-bet expression in developing and established Th2 cells leads to down-regulation of GATA-3 levels.
109	16520391	These findings lead to a model of T cell differentiation that holds that naive T cells tend toward Th2 differentiation through induction of GATA-3 and subsequent down-regulation of STAT4/IL-12Rbeta2 chain unless GATA-3 levels or function is regulated by T-bet.
110	16520391	Thus, the principal function of T-bet in developing Th1 cells is to negatively regulate GATA-3 rather than to positively regulate the IFNG gene.
111	16520391	T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription.
112	16520391	T helper type 1 (Th1) development is facilitated by interrelated changes in key intracellular factors, particularly signal transducer and activator of transcription (STAT)4, T-bet, and GATA-3.
113	16520391	Here we show that CD4+ cells from T-bet-/- mice are skewed toward Th2 differentiation by high endogenous GATA-3 levels but exhibit virtually normal Th1 differentiation provided that GATA-3 levels are regulated at an early stage by anti-interleukin (IL)-4 blockade of IL-4 receptor (R) signaling.
114	16520391	In addition, under these conditions, Th1 cells from T-bet-/- mice manifest IFNG promotor accessibility as detected by histone acetylation and deoxyribonuclease I hypersensitivity.
115	16520391	In related studies, we show that the negative effect of GATA-3 on Th1 differentiation in T-bet-/- cells arises from its ability to suppress STAT4 levels, because if this is prevented by a STAT4-expressing retrovirus, normal Th1 differentiation is observed.
116	16520391	Finally, we show that retroviral T-bet expression in developing and established Th2 cells leads to down-regulation of GATA-3 levels.
117	16520391	These findings lead to a model of T cell differentiation that holds that naive T cells tend toward Th2 differentiation through induction of GATA-3 and subsequent down-regulation of STAT4/IL-12Rbeta2 chain unless GATA-3 levels or function is regulated by T-bet.
118	16520391	Thus, the principal function of T-bet in developing Th1 cells is to negatively regulate GATA-3 rather than to positively regulate the IFNG gene.
119	16520391	T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription.
120	16520391	T helper type 1 (Th1) development is facilitated by interrelated changes in key intracellular factors, particularly signal transducer and activator of transcription (STAT)4, T-bet, and GATA-3.
121	16520391	Here we show that CD4+ cells from T-bet-/- mice are skewed toward Th2 differentiation by high endogenous GATA-3 levels but exhibit virtually normal Th1 differentiation provided that GATA-3 levels are regulated at an early stage by anti-interleukin (IL)-4 blockade of IL-4 receptor (R) signaling.
122	16520391	In addition, under these conditions, Th1 cells from T-bet-/- mice manifest IFNG promotor accessibility as detected by histone acetylation and deoxyribonuclease I hypersensitivity.
123	16520391	In related studies, we show that the negative effect of GATA-3 on Th1 differentiation in T-bet-/- cells arises from its ability to suppress STAT4 levels, because if this is prevented by a STAT4-expressing retrovirus, normal Th1 differentiation is observed.
124	16520391	Finally, we show that retroviral T-bet expression in developing and established Th2 cells leads to down-regulation of GATA-3 levels.
125	16520391	These findings lead to a model of T cell differentiation that holds that naive T cells tend toward Th2 differentiation through induction of GATA-3 and subsequent down-regulation of STAT4/IL-12Rbeta2 chain unless GATA-3 levels or function is regulated by T-bet.
126	16520391	Thus, the principal function of T-bet in developing Th1 cells is to negatively regulate GATA-3 rather than to positively regulate the IFNG gene.
127	17195845	Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells.
128	17195845	Here we show that the transcription factor Runx3 is induced in T helper type 1 (T(H)1) cells in a T-bet-dependent manner, and that both transcription factors T-bet and Runx3 are required for maximal production of interferon-gamma (IFN-gamma) and silencing of the gene encoding interleukin 4 (Il4) in T(H)1 cells.
129	17195845	T-bet does not repress Il4 in Runx3-deficient T(H)2 cells, but coexpression of Runx3 and T-bet induces potent repression in those cells.
130	17195845	Both T-bet and Runx3 bind to the Ifng promoter and the Il4 silencer, and deletion of the silencer decreases the sensitivity of Il4 to repression by either factor.
131	17195845	Our data indicate that cytokine gene expression in T(H)1 cells may be controlled by a feed-forward regulatory circuit in which T-bet induces Runx3 and then 'partners' with Runx3 to direct lineage-specific gene activation and silencing.
132	17195845	Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells.
133	17195845	Here we show that the transcription factor Runx3 is induced in T helper type 1 (T(H)1) cells in a T-bet-dependent manner, and that both transcription factors T-bet and Runx3 are required for maximal production of interferon-gamma (IFN-gamma) and silencing of the gene encoding interleukin 4 (Il4) in T(H)1 cells.
134	17195845	T-bet does not repress Il4 in Runx3-deficient T(H)2 cells, but coexpression of Runx3 and T-bet induces potent repression in those cells.
135	17195845	Both T-bet and Runx3 bind to the Ifng promoter and the Il4 silencer, and deletion of the silencer decreases the sensitivity of Il4 to repression by either factor.
136	17195845	Our data indicate that cytokine gene expression in T(H)1 cells may be controlled by a feed-forward regulatory circuit in which T-bet induces Runx3 and then 'partners' with Runx3 to direct lineage-specific gene activation and silencing.
137	17195845	Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells.
138	17195845	Here we show that the transcription factor Runx3 is induced in T helper type 1 (T(H)1) cells in a T-bet-dependent manner, and that both transcription factors T-bet and Runx3 are required for maximal production of interferon-gamma (IFN-gamma) and silencing of the gene encoding interleukin 4 (Il4) in T(H)1 cells.
139	17195845	T-bet does not repress Il4 in Runx3-deficient T(H)2 cells, but coexpression of Runx3 and T-bet induces potent repression in those cells.
140	17195845	Both T-bet and Runx3 bind to the Ifng promoter and the Il4 silencer, and deletion of the silencer decreases the sensitivity of Il4 to repression by either factor.
141	17195845	Our data indicate that cytokine gene expression in T(H)1 cells may be controlled by a feed-forward regulatory circuit in which T-bet induces Runx3 and then 'partners' with Runx3 to direct lineage-specific gene activation and silencing.
142	17195845	Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells.
143	17195845	Here we show that the transcription factor Runx3 is induced in T helper type 1 (T(H)1) cells in a T-bet-dependent manner, and that both transcription factors T-bet and Runx3 are required for maximal production of interferon-gamma (IFN-gamma) and silencing of the gene encoding interleukin 4 (Il4) in T(H)1 cells.
144	17195845	T-bet does not repress Il4 in Runx3-deficient T(H)2 cells, but coexpression of Runx3 and T-bet induces potent repression in those cells.
145	17195845	Both T-bet and Runx3 bind to the Ifng promoter and the Il4 silencer, and deletion of the silencer decreases the sensitivity of Il4 to repression by either factor.
146	17195845	Our data indicate that cytokine gene expression in T(H)1 cells may be controlled by a feed-forward regulatory circuit in which T-bet induces Runx3 and then 'partners' with Runx3 to direct lineage-specific gene activation and silencing.
147	17195845	Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells.
148	17195845	Here we show that the transcription factor Runx3 is induced in T helper type 1 (T(H)1) cells in a T-bet-dependent manner, and that both transcription factors T-bet and Runx3 are required for maximal production of interferon-gamma (IFN-gamma) and silencing of the gene encoding interleukin 4 (Il4) in T(H)1 cells.
149	17195845	T-bet does not repress Il4 in Runx3-deficient T(H)2 cells, but coexpression of Runx3 and T-bet induces potent repression in those cells.
150	17195845	Both T-bet and Runx3 bind to the Ifng promoter and the Il4 silencer, and deletion of the silencer decreases the sensitivity of Il4 to repression by either factor.
151	17195845	Our data indicate that cytokine gene expression in T(H)1 cells may be controlled by a feed-forward regulatory circuit in which T-bet induces Runx3 and then 'partners' with Runx3 to direct lineage-specific gene activation and silencing.
152	18549798	Janus-kinase-3-dependent signals induce chromatin remodeling at the Ifng locus during T helper 1 cell differentiation.
153	18549798	Differentiation of naive CD4+ T cells into T helper type 1 (Th1) effector cells requires both T cell receptor (TCR) signaling and cytokines such as interleukin-12 and interferon gamma (IFN-gamma).
154	18549798	Here, we report that a third cytokine signal, mediated by the Janus family tyrosine kinase 3 (Jak3) and signal transducer and activator of transcription 5 (STAT5) pathway, is also required for Th1 cell differentiation.
155	18549798	In the absence of Jak3-dependent signals, naive CD4+ T cells proliferate robustly but produce little IFN-gamma after Th1 cell polarization in vitro.
156	18549798	This defect is not due to reduced activation of STAT1 or STAT4 or to impaired upregulation of the transcription factor T-bet.
157	18549798	Instead, we find that T-bet binding to the Ifng promoter is greatly diminished in the absence of Jak3-dependent signals, correlating with a decrease in Ifng promoter accessibility and histone acetylation.
158	18549798	These data indicate that Jak3 regulates epigenetic modification and chromatin remodeling of the Ifng locus during Th1 cell differentiation.
159	18549798	Janus-kinase-3-dependent signals induce chromatin remodeling at the Ifng locus during T helper 1 cell differentiation.
160	18549798	Differentiation of naive CD4+ T cells into T helper type 1 (Th1) effector cells requires both T cell receptor (TCR) signaling and cytokines such as interleukin-12 and interferon gamma (IFN-gamma).
161	18549798	Here, we report that a third cytokine signal, mediated by the Janus family tyrosine kinase 3 (Jak3) and signal transducer and activator of transcription 5 (STAT5) pathway, is also required for Th1 cell differentiation.
162	18549798	In the absence of Jak3-dependent signals, naive CD4+ T cells proliferate robustly but produce little IFN-gamma after Th1 cell polarization in vitro.
163	18549798	This defect is not due to reduced activation of STAT1 or STAT4 or to impaired upregulation of the transcription factor T-bet.
164	18549798	Instead, we find that T-bet binding to the Ifng promoter is greatly diminished in the absence of Jak3-dependent signals, correlating with a decrease in Ifng promoter accessibility and histone acetylation.
165	18549798	These data indicate that Jak3 regulates epigenetic modification and chromatin remodeling of the Ifng locus during Th1 cell differentiation.
166	19050254	T-bet dependent removal of Sin3A-histone deacetylase complexes at the Ifng locus drives Th1 differentiation.
167	19050254	In Th0 cells, histone deacetylase (HDAC)-Sin3A complexes recruited to the Ifng locus actively prevented accumulation of H4 acetylation marks.
168	19050254	Th1 differentiation caused loss of HDAC-Sin3A complexes by T-bet-dependent mechanisms and accumulation of H4 acetylation marks.
169	19050254	T-bet dependent removal of Sin3A-histone deacetylase complexes at the Ifng locus drives Th1 differentiation.
170	19050254	In Th0 cells, histone deacetylase (HDAC)-Sin3A complexes recruited to the Ifng locus actively prevented accumulation of H4 acetylation marks.
171	19050254	Th1 differentiation caused loss of HDAC-Sin3A complexes by T-bet-dependent mechanisms and accumulation of H4 acetylation marks.
172	19332534	Ascaris-infected pigs had increased levels of liver mRNA for T-helper-2 (Th2)-associated cytokines, mast cell markers, and T regulatory (Treg) cells, while infected pigs given ATRA had higher IL4, IL13, CCL11, CCL26, CCL17, CCL22, and TPSB1 expression.
173	19332534	Gene expression for Th1-associated markers (IFNG, IL12B, and TBX21), the CXCR3 ligand (CXCL9), IL1B, and the putative Treg marker TNFRSF18 was also increased.
174	19332534	Expression of IL4, IL13, IL1B, IL6, CCL11, and CCL26 was increased in the lungs of infected pigs treated with ATRA.
175	19332534	IL4 induced CCL11, CCL17, CCL22, and CCL26 mRNA, and ATRA increased the basal and IL4-stimulated expression of CCL17 and CCL22.
176	19384057	Recently, we reported a novel mechanism by which the T-box transcription factor T-bet interacts with JMJD3, an H3K27-demethylase, and Set7/9, an H3K4-methyltransferase (Genes Dev. 2008. 22: 2980-2993).
177	19384057	Therefore, studies examining the molecular mechanisms that account for the ability of T-bet to regulate Ifng and Cxcr3, prototypic CD4+ Th1 genes, have provided novel insight into essential regulatory events that occur at diverse developmental transitions.
178	19384057	Recently, we reported a novel mechanism by which the T-box transcription factor T-bet interacts with JMJD3, an H3K27-demethylase, and Set7/9, an H3K4-methyltransferase (Genes Dev. 2008. 22: 2980-2993).
179	19384057	Therefore, studies examining the molecular mechanisms that account for the ability of T-bet to regulate Ifng and Cxcr3, prototypic CD4+ Th1 genes, have provided novel insight into essential regulatory events that occur at diverse developmental transitions.
180	19464989	In this issue of Immunity, Schulz et al. (2009) use mathematical modeling to elucidate a signaling network controlling Ifng gene expression, thereby showing the importance of an Interleukin-12-dependent, Interferon-gamma-independent second phase of inducing the transcription factor T-bet.
181	19689734	A continuous T-bet expression is required to silence the interleukin-4-producing potential in T helper type 1 cells.
182	19689734	To develop into committed T helper type 1 (Th1) cells, naive CD4(+) T cells not only need to acquire the capacity to produce interferon-gamma (IFN-gamma), but they also need to gain the ability to silence their interleukin-4 (IL-4) -producing potential.
183	19689734	We found that a lack of IL-4 stimulation was not sufficient to silence the IL-4-producing potential in activated CD4(+) T cells and that Th1-promoting factor was required.
184	19689734	Although it has been shown that T-bet is a crucial factor in suppressing Il4 gene expression, it is unclear whether a continuous presence of T-bet is required to silence the Il4 gene in Th1 cells.
185	19689734	To address this problem, we used an inducible form of T-bet - a T-bet-oestrogen receptor fusion molecule (T-bet-ER).
186	19689734	We found that the activation of T-bet during primary or secondary culture was sufficient to silence IL-4-producing potential.
187	19689734	On the other hand, the inactivation of T-bet after naïve CD4(+) T cells had differentiated into Th1 cells resulted in derepression of Il4 gene transcription.
188	19689734	Additionally, we found that T-bet is required to maintain Ifng expression.
189	19689734	Our data demonstrate that the continuous expression of T-bet is required for Th1 cells to silence their IL-4-producing potential.
190	19689734	A continuous T-bet expression is required to silence the interleukin-4-producing potential in T helper type 1 cells.
191	19689734	To develop into committed T helper type 1 (Th1) cells, naive CD4(+) T cells not only need to acquire the capacity to produce interferon-gamma (IFN-gamma), but they also need to gain the ability to silence their interleukin-4 (IL-4) -producing potential.
192	19689734	We found that a lack of IL-4 stimulation was not sufficient to silence the IL-4-producing potential in activated CD4(+) T cells and that Th1-promoting factor was required.
193	19689734	Although it has been shown that T-bet is a crucial factor in suppressing Il4 gene expression, it is unclear whether a continuous presence of T-bet is required to silence the Il4 gene in Th1 cells.
194	19689734	To address this problem, we used an inducible form of T-bet - a T-bet-oestrogen receptor fusion molecule (T-bet-ER).
195	19689734	We found that the activation of T-bet during primary or secondary culture was sufficient to silence IL-4-producing potential.
196	19689734	On the other hand, the inactivation of T-bet after naïve CD4(+) T cells had differentiated into Th1 cells resulted in derepression of Il4 gene transcription.
197	19689734	Additionally, we found that T-bet is required to maintain Ifng expression.
198	19689734	Our data demonstrate that the continuous expression of T-bet is required for Th1 cells to silence their IL-4-producing potential.
199	19689734	A continuous T-bet expression is required to silence the interleukin-4-producing potential in T helper type 1 cells.
200	19689734	To develop into committed T helper type 1 (Th1) cells, naive CD4(+) T cells not only need to acquire the capacity to produce interferon-gamma (IFN-gamma), but they also need to gain the ability to silence their interleukin-4 (IL-4) -producing potential.
201	19689734	We found that a lack of IL-4 stimulation was not sufficient to silence the IL-4-producing potential in activated CD4(+) T cells and that Th1-promoting factor was required.
202	19689734	Although it has been shown that T-bet is a crucial factor in suppressing Il4 gene expression, it is unclear whether a continuous presence of T-bet is required to silence the Il4 gene in Th1 cells.
203	19689734	To address this problem, we used an inducible form of T-bet - a T-bet-oestrogen receptor fusion molecule (T-bet-ER).
204	19689734	We found that the activation of T-bet during primary or secondary culture was sufficient to silence IL-4-producing potential.
205	19689734	On the other hand, the inactivation of T-bet after naïve CD4(+) T cells had differentiated into Th1 cells resulted in derepression of Il4 gene transcription.
206	19689734	Additionally, we found that T-bet is required to maintain Ifng expression.
207	19689734	Our data demonstrate that the continuous expression of T-bet is required for Th1 cells to silence their IL-4-producing potential.
208	19689734	A continuous T-bet expression is required to silence the interleukin-4-producing potential in T helper type 1 cells.
209	19689734	To develop into committed T helper type 1 (Th1) cells, naive CD4(+) T cells not only need to acquire the capacity to produce interferon-gamma (IFN-gamma), but they also need to gain the ability to silence their interleukin-4 (IL-4) -producing potential.
210	19689734	We found that a lack of IL-4 stimulation was not sufficient to silence the IL-4-producing potential in activated CD4(+) T cells and that Th1-promoting factor was required.
211	19689734	Although it has been shown that T-bet is a crucial factor in suppressing Il4 gene expression, it is unclear whether a continuous presence of T-bet is required to silence the Il4 gene in Th1 cells.
212	19689734	To address this problem, we used an inducible form of T-bet - a T-bet-oestrogen receptor fusion molecule (T-bet-ER).
213	19689734	We found that the activation of T-bet during primary or secondary culture was sufficient to silence IL-4-producing potential.
214	19689734	On the other hand, the inactivation of T-bet after naïve CD4(+) T cells had differentiated into Th1 cells resulted in derepression of Il4 gene transcription.
215	19689734	Additionally, we found that T-bet is required to maintain Ifng expression.
216	19689734	Our data demonstrate that the continuous expression of T-bet is required for Th1 cells to silence their IL-4-producing potential.
217	19689734	A continuous T-bet expression is required to silence the interleukin-4-producing potential in T helper type 1 cells.
218	19689734	To develop into committed T helper type 1 (Th1) cells, naive CD4(+) T cells not only need to acquire the capacity to produce interferon-gamma (IFN-gamma), but they also need to gain the ability to silence their interleukin-4 (IL-4) -producing potential.
219	19689734	We found that a lack of IL-4 stimulation was not sufficient to silence the IL-4-producing potential in activated CD4(+) T cells and that Th1-promoting factor was required.
220	19689734	Although it has been shown that T-bet is a crucial factor in suppressing Il4 gene expression, it is unclear whether a continuous presence of T-bet is required to silence the Il4 gene in Th1 cells.
221	19689734	To address this problem, we used an inducible form of T-bet - a T-bet-oestrogen receptor fusion molecule (T-bet-ER).
222	19689734	We found that the activation of T-bet during primary or secondary culture was sufficient to silence IL-4-producing potential.
223	19689734	On the other hand, the inactivation of T-bet after naïve CD4(+) T cells had differentiated into Th1 cells resulted in derepression of Il4 gene transcription.
224	19689734	Additionally, we found that T-bet is required to maintain Ifng expression.
225	19689734	Our data demonstrate that the continuous expression of T-bet is required for Th1 cells to silence their IL-4-producing potential.
226	19689734	A continuous T-bet expression is required to silence the interleukin-4-producing potential in T helper type 1 cells.
227	19689734	To develop into committed T helper type 1 (Th1) cells, naive CD4(+) T cells not only need to acquire the capacity to produce interferon-gamma (IFN-gamma), but they also need to gain the ability to silence their interleukin-4 (IL-4) -producing potential.
228	19689734	We found that a lack of IL-4 stimulation was not sufficient to silence the IL-4-producing potential in activated CD4(+) T cells and that Th1-promoting factor was required.
229	19689734	Although it has been shown that T-bet is a crucial factor in suppressing Il4 gene expression, it is unclear whether a continuous presence of T-bet is required to silence the Il4 gene in Th1 cells.
230	19689734	To address this problem, we used an inducible form of T-bet - a T-bet-oestrogen receptor fusion molecule (T-bet-ER).
231	19689734	We found that the activation of T-bet during primary or secondary culture was sufficient to silence IL-4-producing potential.
232	19689734	On the other hand, the inactivation of T-bet after naïve CD4(+) T cells had differentiated into Th1 cells resulted in derepression of Il4 gene transcription.
233	19689734	Additionally, we found that T-bet is required to maintain Ifng expression.
234	19689734	Our data demonstrate that the continuous expression of T-bet is required for Th1 cells to silence their IL-4-producing potential.
235	19689734	A continuous T-bet expression is required to silence the interleukin-4-producing potential in T helper type 1 cells.
236	19689734	To develop into committed T helper type 1 (Th1) cells, naive CD4(+) T cells not only need to acquire the capacity to produce interferon-gamma (IFN-gamma), but they also need to gain the ability to silence their interleukin-4 (IL-4) -producing potential.
237	19689734	We found that a lack of IL-4 stimulation was not sufficient to silence the IL-4-producing potential in activated CD4(+) T cells and that Th1-promoting factor was required.
238	19689734	Although it has been shown that T-bet is a crucial factor in suppressing Il4 gene expression, it is unclear whether a continuous presence of T-bet is required to silence the Il4 gene in Th1 cells.
239	19689734	To address this problem, we used an inducible form of T-bet - a T-bet-oestrogen receptor fusion molecule (T-bet-ER).
240	19689734	We found that the activation of T-bet during primary or secondary culture was sufficient to silence IL-4-producing potential.
241	19689734	On the other hand, the inactivation of T-bet after naïve CD4(+) T cells had differentiated into Th1 cells resulted in derepression of Il4 gene transcription.
242	19689734	Additionally, we found that T-bet is required to maintain Ifng expression.
243	19689734	Our data demonstrate that the continuous expression of T-bet is required for Th1 cells to silence their IL-4-producing potential.
244	19828627	Ikaros is a regulator of Il10 expression in CD4+ T cells.
245	19828627	Here we show that Ikaros, a zinc finger DNA-binding protein, plays an important role in the regulation of Il10 in murine CD4(+) T cells.
246	19828627	Upon initial stimulation of the TCR, T cells deficient in Ikaros express significantly lower levels of IL-10 compared with wild-type T cells.
247	19828627	In addition, under Th2 skewing conditions, which induce IL-10 production by wild-type T cells, Ikaros null T cells are unable to properly differentiate, producing only low levels of IL-10.
248	19828627	Expression of a dominant-negative isoform of Ikaros in wild-type Th2 cells represses IL-10 production but does not significantly alter expression levels of the genes encoding the transcription factors GATA-3 and T-bet.
249	19828627	Furthermore, expression of Ikaros in Ikaros null T cells restores expression of the Th2 cytokines IL-10 and IL-4 while reducing production of the Th1 cytokine, IFN-gamma.
250	19828627	Coexpression of Ikaros and GATA-3 further increases IL-10 production, showing that these two factors have an additive effect on activating Il10 expression.
251	19828627	Finally, we show that Ikaros binds to conserved regulatory regions of the Il10 gene locus in Th2 cells, supporting a direct role for Ikaros in Il10 expression.
252	19828627	Thus, we provide evidence for Ikaros as a regulator of Il10 and Ifng gene expression and suggest a role for Ikaros in directing lineage-specific cytokine gene activation and repression.
253	19879772	TNFalpha and TGF-beta1 influence IL-18-induced IFNgamma production through regulation of IL-18 receptor and T-bet expression.
254	19879772	IL-18 is a pro-inflammatory cytokine that drives dendritic cell maturation and mediates IFNgamma production.
255	19879772	In this study, we demonstrate that in the dendritic precursor-like cell line KG-1, IFNgamma production induced by IL-18 is potentiated (>5-fold) by TNFalpha and completely suppressed by TGF-beta1.
256	19879772	IL-18 stimulation rapidly activates different MAPK signalling pathways but only blocking of p38 activation alleviates IFNgamma production.
257	19879772	The mechanism through which TNFalpha enhances IL-18 induced IFNgamma production is by promoting IL-18 receptor alpha-chain expression which results in higher levels of p38 activation and induces expression of T-bet, a transcriptional regulator of the IFNG gene.
258	19879772	In contrast, TGF-beta1 rapidly suppresses IFNgamma production by limiting IL-18 receptor numbers at the cell surface and preventing induction of T-bet expression.
259	19879772	TGF-beta1 experience by cells leads to sustained long-term inactivation of TNFalpha/IL-18-mediated cell activation but not IL-18 induced p38 activation suggesting transcriptional silencing of the T-BET and/or IFNG promoter independent of MAPK signalling.
260	19879772	TNFalpha and TGF-beta1 influence IL-18-induced IFNgamma production through regulation of IL-18 receptor and T-bet expression.
261	19879772	IL-18 is a pro-inflammatory cytokine that drives dendritic cell maturation and mediates IFNgamma production.
262	19879772	In this study, we demonstrate that in the dendritic precursor-like cell line KG-1, IFNgamma production induced by IL-18 is potentiated (>5-fold) by TNFalpha and completely suppressed by TGF-beta1.
263	19879772	IL-18 stimulation rapidly activates different MAPK signalling pathways but only blocking of p38 activation alleviates IFNgamma production.
264	19879772	The mechanism through which TNFalpha enhances IL-18 induced IFNgamma production is by promoting IL-18 receptor alpha-chain expression which results in higher levels of p38 activation and induces expression of T-bet, a transcriptional regulator of the IFNG gene.
265	19879772	In contrast, TGF-beta1 rapidly suppresses IFNgamma production by limiting IL-18 receptor numbers at the cell surface and preventing induction of T-bet expression.
266	19879772	TGF-beta1 experience by cells leads to sustained long-term inactivation of TNFalpha/IL-18-mediated cell activation but not IL-18 induced p38 activation suggesting transcriptional silencing of the T-BET and/or IFNG promoter independent of MAPK signalling.
267	19879772	TNFalpha and TGF-beta1 influence IL-18-induced IFNgamma production through regulation of IL-18 receptor and T-bet expression.
268	19879772	IL-18 is a pro-inflammatory cytokine that drives dendritic cell maturation and mediates IFNgamma production.
269	19879772	In this study, we demonstrate that in the dendritic precursor-like cell line KG-1, IFNgamma production induced by IL-18 is potentiated (>5-fold) by TNFalpha and completely suppressed by TGF-beta1.
270	19879772	IL-18 stimulation rapidly activates different MAPK signalling pathways but only blocking of p38 activation alleviates IFNgamma production.
271	19879772	The mechanism through which TNFalpha enhances IL-18 induced IFNgamma production is by promoting IL-18 receptor alpha-chain expression which results in higher levels of p38 activation and induces expression of T-bet, a transcriptional regulator of the IFNG gene.
272	19879772	In contrast, TGF-beta1 rapidly suppresses IFNgamma production by limiting IL-18 receptor numbers at the cell surface and preventing induction of T-bet expression.
273	19879772	TGF-beta1 experience by cells leads to sustained long-term inactivation of TNFalpha/IL-18-mediated cell activation but not IL-18 induced p38 activation suggesting transcriptional silencing of the T-BET and/or IFNG promoter independent of MAPK signalling.
274	19879772	TNFalpha and TGF-beta1 influence IL-18-induced IFNgamma production through regulation of IL-18 receptor and T-bet expression.
275	19879772	IL-18 is a pro-inflammatory cytokine that drives dendritic cell maturation and mediates IFNgamma production.
276	19879772	In this study, we demonstrate that in the dendritic precursor-like cell line KG-1, IFNgamma production induced by IL-18 is potentiated (>5-fold) by TNFalpha and completely suppressed by TGF-beta1.
277	19879772	IL-18 stimulation rapidly activates different MAPK signalling pathways but only blocking of p38 activation alleviates IFNgamma production.
278	19879772	The mechanism through which TNFalpha enhances IL-18 induced IFNgamma production is by promoting IL-18 receptor alpha-chain expression which results in higher levels of p38 activation and induces expression of T-bet, a transcriptional regulator of the IFNG gene.
279	19879772	In contrast, TGF-beta1 rapidly suppresses IFNgamma production by limiting IL-18 receptor numbers at the cell surface and preventing induction of T-bet expression.
280	19879772	TGF-beta1 experience by cells leads to sustained long-term inactivation of TNFalpha/IL-18-mediated cell activation but not IL-18 induced p38 activation suggesting transcriptional silencing of the T-BET and/or IFNG promoter independent of MAPK signalling.
281	20399120	The transcription factor GATA3 actively represses RUNX3 protein-regulated production of interferon-gamma.
282	20399120	The transcription factor GATA3 is crucial for the differentiation of naive CD4(+) T cells into T helper 2 (Th2) cells.
283	20399120	Here, we show that deletion of Gata3 allowed the appearance of interferon-gamma (IFN-gamma)-producing cells in the absence of interleukin-12 (IL-12) and IFN-gamma.
284	20399120	Such IFN-gamma production was transcription factor T-bet independent.
285	20399120	Another T-box-containing transcription factor Eomes, but not T-bet, was induced both in GATA3-deficient CD4(+) T cells differentiated under Th2 cell conditions and in Th2 cells with enforced Runx3 expression, contributing to IFN-gamma production.
286	20399120	GATA3 overexpression blocked Runx3-mediated Eomes induction and IFN-gamma production, and GATA3 protein physically interacted with Runx3 protein.
287	20399120	Furthermore, we found that Runx3 directly bound to multiple regulatory elements of the Ifng gene and that blocking Runx3 function in either Th1 or GATA3-deficient "Th2" cells results in diminished IFN-gamma production by these cells.
288	20399120	Thus, the Runx3-mediated pathway, actively suppressed by GATA3, induces IFN-gamma production in a STAT4- and T-bet-independent manner.
289	20399120	The transcription factor GATA3 actively represses RUNX3 protein-regulated production of interferon-gamma.
290	20399120	The transcription factor GATA3 is crucial for the differentiation of naive CD4(+) T cells into T helper 2 (Th2) cells.
291	20399120	Here, we show that deletion of Gata3 allowed the appearance of interferon-gamma (IFN-gamma)-producing cells in the absence of interleukin-12 (IL-12) and IFN-gamma.
292	20399120	Such IFN-gamma production was transcription factor T-bet independent.
293	20399120	Another T-box-containing transcription factor Eomes, but not T-bet, was induced both in GATA3-deficient CD4(+) T cells differentiated under Th2 cell conditions and in Th2 cells with enforced Runx3 expression, contributing to IFN-gamma production.
294	20399120	GATA3 overexpression blocked Runx3-mediated Eomes induction and IFN-gamma production, and GATA3 protein physically interacted with Runx3 protein.
295	20399120	Furthermore, we found that Runx3 directly bound to multiple regulatory elements of the Ifng gene and that blocking Runx3 function in either Th1 or GATA3-deficient "Th2" cells results in diminished IFN-gamma production by these cells.
296	20399120	Thus, the Runx3-mediated pathway, actively suppressed by GATA3, induces IFN-gamma production in a STAT4- and T-bet-independent manner.
297	20399120	The transcription factor GATA3 actively represses RUNX3 protein-regulated production of interferon-gamma.
298	20399120	The transcription factor GATA3 is crucial for the differentiation of naive CD4(+) T cells into T helper 2 (Th2) cells.
299	20399120	Here, we show that deletion of Gata3 allowed the appearance of interferon-gamma (IFN-gamma)-producing cells in the absence of interleukin-12 (IL-12) and IFN-gamma.
300	20399120	Such IFN-gamma production was transcription factor T-bet independent.
301	20399120	Another T-box-containing transcription factor Eomes, but not T-bet, was induced both in GATA3-deficient CD4(+) T cells differentiated under Th2 cell conditions and in Th2 cells with enforced Runx3 expression, contributing to IFN-gamma production.
302	20399120	GATA3 overexpression blocked Runx3-mediated Eomes induction and IFN-gamma production, and GATA3 protein physically interacted with Runx3 protein.
303	20399120	Furthermore, we found that Runx3 directly bound to multiple regulatory elements of the Ifng gene and that blocking Runx3 function in either Th1 or GATA3-deficient "Th2" cells results in diminished IFN-gamma production by these cells.
304	20399120	Thus, the Runx3-mediated pathway, actively suppressed by GATA3, induces IFN-gamma production in a STAT4- and T-bet-independent manner.
305	20921622	Enhanced cell cycle and metabolic activity was restricted to the acute phase of the response, but at all stages, HCMV-specific CD8+ T cells expressed the Th1-associated transcription factors T-bet (TBX21) and eomesodermin (EOMES), in parallel with continuous expression of IFNG mRNA and IFN-γ-regulated genes.
306	20921622	The cytolytic proteins granzyme B and perforin as well as the fractalkine-binding chemokine receptor CX3CR1 were found in virus-reactive cells throughout the response.
307	21095589	Jmjd3 and UTX play a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression.
308	21095589	In this study, we show that the H3K27 demethylases, Jmjd3 and UTX, mediate a functional interaction between the lineage-defining T-box transcription factor family and a Brg1-containing SWI/SNF remodeling complex.
309	21095589	Importantly, Jmjd3 is required for the coprecipitation of Brg1 with the T-box factor, T-bet, and this interaction is necessary for Ifng remodeling in differentiated Th1 cells.
310	21321581	Protection against diabetes was accompanied by histone hyperacetylation in pancreas and spleen, enhanced frequency of CD4(+) CD62L(+) cells in the spleen, reduction in cellular infiltration of islets, restoration of normoglycemia and glucose-induced insulin release by beta cells.
311	21321581	Activation of splenic T lymphocytes derived from protected mice in vitro with pharmacological agents that bypass the antigen receptor or immobilized anti-CD3 antibody resulted in enhanced expression of Ifng mRNA and protein without altering the expression of Il4, Il17, Il18, Inos and Tnfa genes nor the secretion of IL-2, IL-4, IL-17 and TNF-α proteins.
312	21321581	Consistently, expression of the transcription factor involved in Ifng transcription, Tbet/Tbx21 but not Gata3 and Rorgt, respectively, required for the transcription of Il4 and Il17, was upregulated in activated splenocytes of protected mice.
313	21480212	Rapamycin-sensitive signals control TCR/CD28-driven Ifng, Il4 and Foxp3 transcription and promoter region methylation.
314	21480212	Here, we report that both mTOR complex 1 and mTOR complex 2 are readily activated following TCR/CD28 engagement and are critical for early expression of Ifng, Il4 and Foxp3, and for effector T cell differentiation in the absence of polarizing cytokines.
315	21480212	While inhibition of mTOR complex 1 and cell division were evident at low doses of RAPA, inhibition of mTOR complex 2, Ifng, Il4 and Foxp3 expression, and T-cell polarization required higher doses and more prolonged treatments.
316	21480212	We found that while T-bet and GATA3 were readily induced following TCR/CD28 engagement, administration of RAPA delayed their expression, and interfered with the loss of DNA methylation within Ifng and Il4 promoter regions.
317	21518797	The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns.
318	21518797	The T-box transcription factor T-bet is important for the differentiation of naive CD4(+) T helper cells (Th cells) into the Th1 phenotype.
319	21518797	In this study, we first identify Socs1, Socs3, and Tcf7 (TCF-1) as gene targets that are negatively regulated by T-bet.
320	21518797	Consistent with this, we identified two T-bet DNA-binding elements in the Socs1 promoter that are functionally used to down-regulate transcription in primary Th1 cells.
321	21518797	Furthermore, T-bet functionally recruits Bcl-6 to the Ifng locus in late stages of Th1 differentiation to repress its activity, possibly to prevent the overproduction of IFN-γ, which could result in autoimmunity.
322	21518797	The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns.
323	21518797	The T-box transcription factor T-bet is important for the differentiation of naive CD4(+) T helper cells (Th cells) into the Th1 phenotype.
324	21518797	In this study, we first identify Socs1, Socs3, and Tcf7 (TCF-1) as gene targets that are negatively regulated by T-bet.
325	21518797	Consistent with this, we identified two T-bet DNA-binding elements in the Socs1 promoter that are functionally used to down-regulate transcription in primary Th1 cells.
326	21518797	Furthermore, T-bet functionally recruits Bcl-6 to the Ifng locus in late stages of Th1 differentiation to repress its activity, possibly to prevent the overproduction of IFN-γ, which could result in autoimmunity.
327	21518797	The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns.
328	21518797	The T-box transcription factor T-bet is important for the differentiation of naive CD4(+) T helper cells (Th cells) into the Th1 phenotype.
329	21518797	In this study, we first identify Socs1, Socs3, and Tcf7 (TCF-1) as gene targets that are negatively regulated by T-bet.
330	21518797	Consistent with this, we identified two T-bet DNA-binding elements in the Socs1 promoter that are functionally used to down-regulate transcription in primary Th1 cells.
331	21518797	Furthermore, T-bet functionally recruits Bcl-6 to the Ifng locus in late stages of Th1 differentiation to repress its activity, possibly to prevent the overproduction of IFN-γ, which could result in autoimmunity.
332	21518797	The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns.
333	21518797	The T-box transcription factor T-bet is important for the differentiation of naive CD4(+) T helper cells (Th cells) into the Th1 phenotype.
334	21518797	In this study, we first identify Socs1, Socs3, and Tcf7 (TCF-1) as gene targets that are negatively regulated by T-bet.
335	21518797	Consistent with this, we identified two T-bet DNA-binding elements in the Socs1 promoter that are functionally used to down-regulate transcription in primary Th1 cells.
336	21518797	Furthermore, T-bet functionally recruits Bcl-6 to the Ifng locus in late stages of Th1 differentiation to repress its activity, possibly to prevent the overproduction of IFN-γ, which could result in autoimmunity.
337	21518797	The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns.
338	21518797	The T-box transcription factor T-bet is important for the differentiation of naive CD4(+) T helper cells (Th cells) into the Th1 phenotype.
339	21518797	In this study, we first identify Socs1, Socs3, and Tcf7 (TCF-1) as gene targets that are negatively regulated by T-bet.
340	21518797	Consistent with this, we identified two T-bet DNA-binding elements in the Socs1 promoter that are functionally used to down-regulate transcription in primary Th1 cells.
341	21518797	Furthermore, T-bet functionally recruits Bcl-6 to the Ifng locus in late stages of Th1 differentiation to repress its activity, possibly to prevent the overproduction of IFN-γ, which could result in autoimmunity.
342	21983879	T-bet orchestrates the differentiation of mature peripheral T-cells into interferon-γ (IFN-γ) and tumor necrosis factor-α producing CD4+ T-helper type I (Th1) and CD8+ T cytotoxic cells that are necessary for antiviral responses.
343	21983879	When IL-12 is produced by antigen-presenting cells, T-bet expression is induced, causing direct stimulation of ifng gene transcription while simultaneously acting as a transcriptional repressor of the IL4 gene, which then leads to Th1 dominance and T-helper type 2 differentiation blockade.
344	21983879	We found that treatment with a farnesyltransferase inhibitor tipifarnib reduced Th1 cytokines in LGL leukemia patient T-cells and blocked T-bet protein expression and IL-12 responsiveness in T-cells from healthy donors.
345	21983879	T-bet orchestrates the differentiation of mature peripheral T-cells into interferon-γ (IFN-γ) and tumor necrosis factor-α producing CD4+ T-helper type I (Th1) and CD8+ T cytotoxic cells that are necessary for antiviral responses.
346	21983879	When IL-12 is produced by antigen-presenting cells, T-bet expression is induced, causing direct stimulation of ifng gene transcription while simultaneously acting as a transcriptional repressor of the IL4 gene, which then leads to Th1 dominance and T-helper type 2 differentiation blockade.
347	21983879	We found that treatment with a farnesyltransferase inhibitor tipifarnib reduced Th1 cytokines in LGL leukemia patient T-cells and blocked T-bet protein expression and IL-12 responsiveness in T-cells from healthy donors.
348	21983879	T-bet orchestrates the differentiation of mature peripheral T-cells into interferon-γ (IFN-γ) and tumor necrosis factor-α producing CD4+ T-helper type I (Th1) and CD8+ T cytotoxic cells that are necessary for antiviral responses.
349	21983879	When IL-12 is produced by antigen-presenting cells, T-bet expression is induced, causing direct stimulation of ifng gene transcription while simultaneously acting as a transcriptional repressor of the IL4 gene, which then leads to Th1 dominance and T-helper type 2 differentiation blockade.
350	21983879	We found that treatment with a farnesyltransferase inhibitor tipifarnib reduced Th1 cytokines in LGL leukemia patient T-cells and blocked T-bet protein expression and IL-12 responsiveness in T-cells from healthy donors.
351	22019771	We used a gene panel of regulatory/inflammatory molecules (FOXP3, GATA3, IL10, TGFB1, TGFBR1/ TBX21, TNF and IFNG) to investigate the gene expression profile in peripheral blood mononuclear cells of renal-transplanted individuals experiencing OT compared to transplanted individuals not displaying OT and healthy individuals (HI).
352	22019771	OT subjects showed a predominant regulatory (REG) profile with higher gene expression of GATA3, FOXP3, TGFB1 and TGFB receptor 1 compared to the other groups.
353	22685315	Twist1 regulates Ifng expression in Th1 cells by interfering with Runx3 function.
354	22685315	A transcription factor network that includes STAT4, T-bet, and Runx3 promotes the differentiation of Th1 cells and inflammatory immune responses.
355	22685315	In this study we show that the negative regulatory factor Twist1 decreases expression of T-bet, Runx3, and IL-12Rβ2 as it inhibits IFN-γ production.
356	22685315	Ectopic expression of Runx3, but not T-bet or IL-12Rβ2, compensates for the effects of Twist1 on IFN-γ production, and Twist1 regulation of Ifng depends on complex formation with Runx3.
357	22685315	Twist1 decreases Runx3 and T-bet binding at the Ifng locus, and it decreases chromatin looping within the Ifng locus.
358	22685315	These data define an IL-12/STAT4-induced negative regulatory loop that impacts multiple components of the Th1 transcriptional network and provide further insight into regulation of Th1 differentiation.
359	22685315	Twist1 regulates Ifng expression in Th1 cells by interfering with Runx3 function.
360	22685315	A transcription factor network that includes STAT4, T-bet, and Runx3 promotes the differentiation of Th1 cells and inflammatory immune responses.
361	22685315	In this study we show that the negative regulatory factor Twist1 decreases expression of T-bet, Runx3, and IL-12Rβ2 as it inhibits IFN-γ production.
362	22685315	Ectopic expression of Runx3, but not T-bet or IL-12Rβ2, compensates for the effects of Twist1 on IFN-γ production, and Twist1 regulation of Ifng depends on complex formation with Runx3.
363	22685315	Twist1 decreases Runx3 and T-bet binding at the Ifng locus, and it decreases chromatin looping within the Ifng locus.
364	22685315	These data define an IL-12/STAT4-induced negative regulatory loop that impacts multiple components of the Th1 transcriptional network and provide further insight into regulation of Th1 differentiation.
365	22685315	Twist1 regulates Ifng expression in Th1 cells by interfering with Runx3 function.
366	22685315	A transcription factor network that includes STAT4, T-bet, and Runx3 promotes the differentiation of Th1 cells and inflammatory immune responses.
367	22685315	In this study we show that the negative regulatory factor Twist1 decreases expression of T-bet, Runx3, and IL-12Rβ2 as it inhibits IFN-γ production.
368	22685315	Ectopic expression of Runx3, but not T-bet or IL-12Rβ2, compensates for the effects of Twist1 on IFN-γ production, and Twist1 regulation of Ifng depends on complex formation with Runx3.
369	22685315	Twist1 decreases Runx3 and T-bet binding at the Ifng locus, and it decreases chromatin looping within the Ifng locus.
370	22685315	These data define an IL-12/STAT4-induced negative regulatory loop that impacts multiple components of the Th1 transcriptional network and provide further insight into regulation of Th1 differentiation.
371	22685315	Twist1 regulates Ifng expression in Th1 cells by interfering with Runx3 function.
372	22685315	A transcription factor network that includes STAT4, T-bet, and Runx3 promotes the differentiation of Th1 cells and inflammatory immune responses.
373	22685315	In this study we show that the negative regulatory factor Twist1 decreases expression of T-bet, Runx3, and IL-12Rβ2 as it inhibits IFN-γ production.
374	22685315	Ectopic expression of Runx3, but not T-bet or IL-12Rβ2, compensates for the effects of Twist1 on IFN-γ production, and Twist1 regulation of Ifng depends on complex formation with Runx3.
375	22685315	Twist1 decreases Runx3 and T-bet binding at the Ifng locus, and it decreases chromatin looping within the Ifng locus.
376	22685315	These data define an IL-12/STAT4-induced negative regulatory loop that impacts multiple components of the Th1 transcriptional network and provide further insight into regulation of Th1 differentiation.
377	22685317	Naturally occurring effector CD8(+) T cells, with a KLRG1(hi) CD62L(lo) phenotype typical of short-lived effector CD8(+) T cells (SLECs), can be found in increased numbers in autoimmune-prone mice, most notably in mice homozygous for the san allele of Roquin.
378	22685317	When Roquin is mutated (Roquin(san)), effector CD8(+) T cells accumulate in a cell-autonomous manner, most prominently as SLEC-like effectors.
379	22685317	Excessive IFN-γ promotes the accumulation of SLEC-like cells, increases their T-bet expression, and enhances their granzyme B production in vivo.
380	22685317	This study identifies a novel mechanism that prevents accumulation of self-reactive cytotoxic effectors, highlighting the importance of regulating Ifng mRNA stability to maintain CD8(+) T cell homeostasis and prevent CD8-mediated autoimmunity.
381	22851706	In this study, we show that transcription of both mouse and human TMEVPG1 genes is Th1 selective and dependent on Stat4 and T-bet, transcription factors that drive the Th1 differentiation program.
382	22851706	Ifng expression is partially restored in Stat4-/-Tbx21-/- cells through coexpression of T-bet and Tmevpg1, and Tmevpg1 expression contributes to, but alone is not sufficient to, drive Th1-dependent Ifng expression.
383	22851706	In this study, we show that transcription of both mouse and human TMEVPG1 genes is Th1 selective and dependent on Stat4 and T-bet, transcription factors that drive the Th1 differentiation program.
384	22851706	Ifng expression is partially restored in Stat4-/-Tbx21-/- cells through coexpression of T-bet and Tmevpg1, and Tmevpg1 expression contributes to, but alone is not sufficient to, drive Th1-dependent Ifng expression.
385	23159227	Unlike ICOS and T-bet deficiency that failed to rescue several autoimmune manifestations, interferon-γ receptor (IFN-γR) deficiency prevented lupus development.
386	23668260	The infected mice displayed a significant up-regulation in the expression of chemokines (Cxcl1, Cxcl2 and Ccl2), numerous pro-inflammatory cytokines (Ifng, Il1b, Il6, and Il17f), as well as Il22 and a number of anti-microbial peptides (Defa1, Defa28, Defb1, Slpi and Reg3g) at the site(s) of infection.
387	23668260	However, CD4 T cells of the untreated and C. difficile-infected mice expressed similar levels of CD69 and CD25.
388	23668260	Neither tissue had up-regulated levels of Tbx21, Gata3 or Rorc.
389	23668260	They also displayed significantly higher phosphorylation of AKT and signal transducer and activator of transcription 3 (STAT3), an indication of pro-survival signalling.
390	23668260	These data underscore the local, innate, pro-inflammatory nature of the response to C. difficile and highlight eIF2α phosphorylation and the interleukin-22-pSTAT3-RegIIIγ axis as two of the pathways that could be used to contain and counteract the damage inflicted on the intestinal epithelium.
391	23761633	STAT4 and T-bet are required for the plasticity of IFN-γ expression across Th2 ontogeny and influence changes in Ifng promoter DNA methylation.
392	23761633	CD4(+) T cells developing toward a Th2 fate express IL-4, IL-5, and IL-13 while inhibiting production of cytokines associated with other Th types, such as the Th1 cytokine IFN- γ.
393	23761633	We now show that this flexibility ("plasticity") of cytokine expression is preceded by a loss of the repressive DNA methylation of the Ifng promoter acquired during Th2 polarization yet requires STAT4 along with T-box expressed in T cells.
394	23761633	Surprisingly, loss of either STAT4 or T-box expressed in T cells increased Ifng promoter CpG methylation in both effector and memory Th2 cells.
395	23761633	STAT4 and T-bet are required for the plasticity of IFN-γ expression across Th2 ontogeny and influence changes in Ifng promoter DNA methylation.
396	23761633	CD4(+) T cells developing toward a Th2 fate express IL-4, IL-5, and IL-13 while inhibiting production of cytokines associated with other Th types, such as the Th1 cytokine IFN- γ.
397	23761633	We now show that this flexibility ("plasticity") of cytokine expression is preceded by a loss of the repressive DNA methylation of the Ifng promoter acquired during Th2 polarization yet requires STAT4 along with T-box expressed in T cells.
398	23761633	Surprisingly, loss of either STAT4 or T-box expressed in T cells increased Ifng promoter CpG methylation in both effector and memory Th2 cells.
399	23761633	STAT4 and T-bet are required for the plasticity of IFN-γ expression across Th2 ontogeny and influence changes in Ifng promoter DNA methylation.
400	23761633	CD4(+) T cells developing toward a Th2 fate express IL-4, IL-5, and IL-13 while inhibiting production of cytokines associated with other Th types, such as the Th1 cytokine IFN- γ.
401	23761633	We now show that this flexibility ("plasticity") of cytokine expression is preceded by a loss of the repressive DNA methylation of the Ifng promoter acquired during Th2 polarization yet requires STAT4 along with T-box expressed in T cells.
402	23761633	Surprisingly, loss of either STAT4 or T-box expressed in T cells increased Ifng promoter CpG methylation in both effector and memory Th2 cells.
403	24120504	In biofunction assays, recombinant gCCL4 was found to induce chemotactic activity in the peripheral blood leukocytes of groupers and up-regulate the gene expressions of grouper TNFA1 (TNF-α1), TNFA2 (TNF-α2), IFNG (IFN-γ), MX, TBX21 (T-bet), CD8 (α and β chain).
404	24249741	SerpinB1 regulates homeostatic expansion of IL-17+ γδ and CD4+ Th17 cells.
405	24249741	Here, we show that IL-17A(+) γδ and CD4(+) Th17 cells are already expanded in the lungs of serpinb1a(-/-) mice at steady-state.
406	24249741	Both γδ and αβ(+) CD4(+) CCR6(+) T cells isolated from the lungs of naive serpinb1a(-/-) mice displayed a skewed transcriptional profile relative to WT cells, including increased Th17 signature transcripts [Il17a, l17f, and Rorc (RORγt)] and decreased Th1 signature transcripts [Ifng, Cxcr3, and Tbx21 (T-bet)] in γδ T cells.
407	24249741	In addition to the lung, IL-17A(+) γδ and CD4(+) Th17 cells were increased in the spleen of naive serpinb1a(-/-) mice, despite normal αβ and γδ T cell development in the thymus.
408	24249741	Within the γδ T cell compartment, loss of serpinb1a prompted selective expansion of Vγ4(+) and Vγ6/Vδ1(+) cells, which also displayed elevated expression of the proliferating cell nuclear antigen, Ki-67, and IL-17A.
409	24249741	Given that serpinb1a is preferentially expressed in WT IL-17A(+) γδ and CD4(+) Th17 cell subsets vis-à-vis other T cell lineages, our findings reveal a novel function of serpinB1 in limiting untoward expansion of lymphocytes with a Th17 phenotype.
410	24296812	TNF-α(+) and IFN-γ(+) CD4(+) T cells expressed significantly higher levels of T-box transcription factors T-bet with graded loss of Eomesodermin (Eomes) expression (T-bet(Hi)Eomes(Hi/Lo)) when compared with TNF-α(+) CD4(+) T cells expressing lower levels of both T-bet and Eomes (T-bet(-)Eomes(-)).
411	24296812	Furthermore, TNF-α(+) and IFN-γ(+) CD4(+) T cells expressed significantly higher levels of perforin and interleukin (IL)-2 and displayed a terminally differentiated phenotype (CCR7(-)CD27(-)CD45RA(-)CD57(+)CD62L(-)).
412	24296812	In contrast, TNF-α(+) alone CMV-specific CD4(+) T cells were predominantly early-memory phenotype with a proportion of these cells displaying T memory stem-cell phenotype (CD95(+)CD45RA(+)CCR7(+)CD27(+)).
413	24296812	In vitro stimulation of CMV-specific CD4(+) T cells with viral antigen in the presence of IL-12 was sufficient to dramatically change the transcriptional and functional profile of TNF-α(+) CD4(+) T cells, whereas TNF-α(+) and IFN-γ(+) CD4(+) T cells remained unaltered.