biostudies-literatureZhu JIntramural NIH HHS660-73https://www.ebi.ac.uk/biostudies/studies/S-EPMC3717271biostudies-literatureUnknown37(4)T-bet is a critical transcription factor for T helper 1 (Th1) cell differentiation. To study the regulation and functions of T-bet, we developed a T-bet-ZsGreen reporter mouse strain. We determined that interleukin-12 (IL-12) and interferon-? (IFN-?) were redundant in inducing T-bet in mice infected with Toxoplasma gondii and that T-bet did not contribute to its own expression when induced by IL-12 and IFN-?. By contrast, T-bet and the transcription factor Stat4 were critical for IFN-? production whereas IFN-? signaling was dispensable for inducing IFN-?. Loss of T-bet resulted in activation of an endogenous program driving Th2 cell differentiation in cells expressing T-bet-ZsGreen. Genome-wide analyses indicated that T-bet directly induced many Th1 cell-related genes but indirectly suppressed Th2 cell-related genes. Our study revealed redundancy and synergy among several Th1 cell-inducing pathways in regulating the expression of T-bet and IFN-?, and a critical role of T-bet in suppressing an endogenous Th2 cell-associated program.ImmunityThe transcription factor T-bet is induced by multiple pathways and prevents an endogenous Th2 cell program during Th1 cell responses.PMC3717271ZIA AI001169-01Punkosdy GOler AJSharma SJankovic DFeigenbaum LGuo LZhu JYamane HHu GYagi RWei GZhao KPaul WEfalseThe transcription factor T-bet is induced by multiple pathways and prevents an endogenous Th2 cell program during Th1 cell responses.T-bet is a critical transcription factor for T helper 1 (Th1) cell differentiation. To study the regulation and functions of T-bet, we developed a T-bet-ZsGreen reporter mouse strain. We determined that interleukin-12 (IL-12) and interferon-? (IFN-?) were redundant in inducing T-bet in mice infected with Toxoplasma gondii and that T-bet did not contribute to its own expression when induced by IL-12 and IFN-?. By contrast, T-bet and the transcription factor Stat4 were critical for IFN-? production whereas IFN-? signaling was dispensable for inducing IFN-?. Loss of T-bet resulted in activation of an endogenous program driving Th2 cell differentiation in cells expressing T-bet-ZsGreen. Genome-wide analyses indicated that T-bet directly induced many Th1 cell-related genes but indirectly suppressed Th2 cell-related genes. Our study revealed redundancy and synergy among several Th1 cell-inducing pathways in regulating the expression of T-bet and IFN-?, and a critical role of T-bet in suppressing an endogenous Th2 cell-associated program.2012-01-01T00:00:00Z2012 Oct2020-10-31T09:27:02Z2019-03-27T01:13:22ZS-EPMC37172712304106410.1016/j.immuni.2012.09.007