Tet2-mediated epigenetic programing of T follicular helper cell differentiation (RNA-Seq)

Tet2-mediated demethylation is a key component of epigenetic programing that promotes lineage specific gene expression and contributes to cellular differentiation and function. While the differentiation of CD4+ T cell subsets has been studied extensively, the epigenetic programs that regulate these processes remain unclear. We report that Tet2 acts to restrict the differentiation of T follicular helper (Tfh) cells in CD4+ T cells responding to viral infection. Tet2-deficient CD4+ T cells preferentially differentiated into highly functional germinal center (GC) Tfh cells that provided enhanced help for B cell responses. Using genome-wide expression and methylation analyses combined with Foxo1 ChIPseq analysis, we found that Tet2 coordinates with multiple transcription factors, including Foxo1, to mediate the demethylation and expression of their target genes following activation. Mouse antigen specific WT and Tet2KO CD4+ T cells (SMARTA TCR Transgenic) were sorted from spleens of non-infected mice (CD4+ T cell naïve samples) and LCMV Armstrong infected mice at 7 days post infection (effector Th1 and effector Tfh samples) for RNAsequencing