IL-1R signaling promotes STAT3 and NF-κB factor recruitment to distal cis-regulatory elements that regulate Il17a/f transcription.

Journal Article (Journal Article)

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 both proximal signaling events and downstream interactions between transcription factors and cis-regulatory elements to promote Il17a/f transcription and Th17 differentiation.

Full Text

Duke Authors

Cited Authors

  • Whitley, SK; Balasubramani, A; Zindl, CL; Sen, R; Shibata, Y; Crawford, GE; Weathington, NM; Hatton, RD; Weaver, CT

Published Date

  • October 12, 2018

Published In

Volume / Issue

  • 293 / 41

Start / End Page

  • 15790 - 15800

PubMed ID

  • 30093408

Pubmed Central ID

  • PMC6187645

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

Digital Object Identifier (DOI)

  • 10.1074/jbc.RA118.002721


  • eng

Conference Location

  • United States