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Learn MoreHost 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. SOURCE: Fred,P.,Davis (Fred.davis@nih.gov) - NIH
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