TH17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity

Stacey N. Harbour, Daniel F. Ditoro, Steven J. Witte, Carlene L. Zindl, Min Gao, Trenton R. Schoeb, Gareth W. Jones, Simon A. Jones, Robin D. Hatton, Casey T. Weaver*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

13 Downloads (Pure)

Abstract

Acting in concert with TGF-β, interleukin-6 (IL-6) signaling induces T helper 17 (TH17) cell development by programming TH17-related genes via signal transducers and activators of transcription 3 (STAT3). A role for IL-6 signaling beyond the inductive phase of TH17 cell development has not been defined because IL-23 signaling downstream of TH17 cell induction also activates STAT3 and is thought responsible for TH17 cell maintenance. Here, we find that IL-6 signaling is required for both induction and maintenance of mouse TH17 cells; IL-6Rα–deficient TH17 cells rapidly lost their TH17 phenotype and did not cause disease in two models of colitis. Cotransfer of wild-type TH17 cells with IL-6Rα–deficient TH17 cells induced colitis but was unable to rescue phenotype loss of the latter. High IL-6 expression in the colon promoted classic, or cis, rather than transreceptor signaling that was required for maintenance of TH17 cells. Thus, ongoing classic IL-6 signaling underpins the TH17 program and is required for TH17 cell maintenance and function.
Original languageEnglish
Pages (from-to)eaaw2262
JournalScience Immunology
Volume5
Issue number49
DOIs
Publication statusPublished - 17 Jul 2020

Fingerprint Dive into the research topics of 'TH17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity'. Together they form a unique fingerprint.

Cite this