The transcription factor T-bet is induced by multiple pathways and prevents an endogenous Th2 cell program during Th1 cell responses.

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.

SUBMITTER: Zhu J 

PROVIDER: S-EPMC3717271 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature