Pluto Bioinformatics

GSE103173: The transcription factor Bhlhe40 is a switch of inflammatory versus anti-inflammatory Th1 cell fate determination

Bulk RNA sequencing

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 anti-inflammatory through producing IL-10. However, the molecular switch for regulating the differentiation of inflammatory and anti-inflammatory 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. 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 blockage 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 anti-inflammatory Th1 cells. SOURCE: Gangqing HuSystems Biology Center NIH