The transcription factor Bhlhe40 is a switch of inflammatory versus antiinflammatory Th1 cell fate determination.

ABSTRACT: Type 1 T helper (Th1) cells play a critical role in host defense against intracellular pathogens and in autoimmune diseases by producing a key inflammatory cytokine interferon (IFN)-?; some Th1 cells can also be antiinflammatory through producing IL-10. However, the molecular switch for regulating the differentiation of inflammatory and antiinflammatory Th1 cells is still elusive. Here, we show that Bhlhe40-deficient CD4 Th1 cells produced less IFN-? but substantially more IL-10 than wild-type Th1 cells both in vitro and in vivo. Bhlhe40-mediated IFN-? production was independent of transcription factor T-bet regulation. Mice with conditional deletion of Bhlhe40 in T cells succumbed to Toxoplasma gondii infection, and blockade of IL-10 signaling during infection rescued these mice from death. Thus, our results demonstrate that transcription factor Bhlhe40 is a molecular switch for determining the fate of inflammatory and antiinflammatory Th1 cells.

SUBMITTER: Yu F 

PROVIDER: S-EPMC6028509 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature