GSE96724
The Transcription Factor T-bet Limits Amplification of Type I IFN Transcriptome and Circuitry in T Helper 1 Cells
Host defense requires the specification of CD4+ helper T (Th) cells into distinct fates including Th1 cells that preferentially produce interferon ??(IFN-?  ).?IFN-?  , a member of a large family of anti-pathogenic and anti-tumor IFNs, induces T-bet, a lineage defining transcription factor for Th1 cells, which in turn supports IFN-?   production in a feed-forward manner. Herein, we show a cell intrinsic role of T- bet to influence how T cells perceive their secreted product in the environment. In the absence of T-bet, IFN-?   aberrantly induces a type I IFN transcriptomic program. T-bet preferentially represses genes and pathways ordinarily activated by type I IFNs to ensure that its transcriptional response does not evoke an aberrant amplification of type I IFN signaling circuitry otherwise triggered by its own product. Overall design: Integrated analysis of epigenome and transcriptome data from activated T helper cells cultured under either IFN-?  or IFN-ß stimulation