The transcriptional repressor Gfi1 inhibits the induction of Th1 program in activated CD4 T cells [ChIP-seq]

The transcriptional repressor Gfi1 promotes Th2 cell development and inhibits Th17 and inducible regulatory T cell differentiation. However, the contribution of Gfi1 to Th1 cell differentiation and Th1-type immune responses has not been clarified yet. We herein demonstrate that Gfi1 inhibits the activation of Th1 program in CD4 T cells. The activated Gfi1-deficient naïve CD4 T cells spontaneously develop into Th1 cells in an IL-12- and IFN-g-independent manner. The increased in vivo Th1-type immune response in Gfi1-deficient mice is confirmed using murine model of nickel allergy and delayed-type hypersensitivity. The expressions of Th1-related transcription factors including Tbx21, Eomes, Atf3, Runx1, Runx2 and Runx3 are increased in Gfi1-deficient activated CD4 T cells. Tbx21, Eomes and Runx2 are identified as candidates for direct target of Gfi1. Gfi1 binds to the Tbx21, Eomes and Runx2 gene loci and represses histone H3K4 methylation levels. Together, these findings establish a novel role of Gfi1 in inhibiting Th1 cell differentiation and Th1-type immune response. Overall design: Examination of Gfi1 binding in WT and Gfi1-dficient CD4 T cells