{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhu J"],"funding":["Intramural NIH HHS"],"pagination":["660-73"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3717271"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["37(4)"],"pubmed_abstract":["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."],"journal":["Immunity"],"pubmed_title":["The transcription factor T-bet is induced by multiple pathways and prevents an endogenous Th2 cell program during Th1 cell responses."],"pmcid":["PMC3717271"],"funding_grant_id":["ZIA AI001169-01"],"pubmed_authors":["Punkosdy G","Oler AJ","Sharma S","Jankovic D","Feigenbaum L","Guo L","Zhu J","Yamane H","Hu G","Yagi R","Wei G","Zhao K","Paul WE"],"additional_accession":[]},"is_claimable":false,"name":"The transcription factor T-bet is induced by multiple pathways and prevents an endogenous Th2 cell program during Th1 cell responses.","description":"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.","dates":{"release":"2012-01-01T00:00:00Z","publication":"2012 Oct","modification":"2020-10-31T09:27:02Z","creation":"2019-03-27T01:13:22Z"},"accession":"S-EPMC3717271","cross_references":{"pubmed":["23041064"],"doi":["10.1016/j.immuni.2012.09.007"]}}