IL-1R signaling promotes STAT3 and NF-{kappa}B factor recruitment to distal cis-regulatory elements that regulate Il17a/f transcription [Gene Regulation]

Interleukin (IL)-1β plays a critical role in IL-6β– and transforming growth factor β (TGFβ)–initiated Th17 differentiation and induction of Th17-mediated autoimmunity. However, the means by which IL-1 regulates various aspects of Th17 development remain poorly understood. We recently reported that IL-1β enhances STAT3 phosphorylation via NF-κB–mediated repression of SOCS3 to facilitate Il17 transcription and Th17 differentiation, identifying an effect of IL-1 signaling on proximal events of STAT3 signaling. Here, we show that IL-1β promotes STAT3 binding to key cis-elements that control IL-17 expression. Additionally, we demonstrate that the IL-1–induced NF-κB factor RelA directly regulates the Il17a/f loci in cooperation with STAT3. Our findings reveal that IL-1 impacts bo...

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