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Th17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity

Harbour, Stacey N., DiToro, Daniel F., Witte, Steven J., Zindl, Carlene L., Gao, Min, Schoeb, Trenton R., Jones, Gareth W., Jones, Simon, Hatton, Robin D. and Weaver, Casey T. 2020. Th17 cells require ongoing classic IL-6 receptor signaling to retain transcriptional and functional identity. Science Immunology 5 (49) , eaaw2262. 10.1126/sciimmunol.aaw2262

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Abstract

Acting in concert with TGF-b, IL-6 signaling induces Th17 cell development by programming Th17-related genes via STAT3. A role for IL-6 signaling beyond the inductive phase of Th17 cell development has not been defined, as 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 Th17 cells; IL-6Ra–deficient Th17 cells rapidly lost their Th17 phenotype and did not cause disease in two models of colitis. Cotransfer of WT Th17 cells with IL-6Ra–deficient Th17 cells induced colitis but was unable to rescue phenotype loss of the latter. High IL-6 in the colon promoted classic, or cis, rather than trans receptor signaling that was required for maintenance of Th17 cells. Thus, ongoing classic IL6 signaling underpins the Th17 program and is required for Th17 cell maintenance and function.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > RB Pathology
Publisher: American Association for the Advancement of Science
ISSN: 2470-9468
Funders: Versus Arthritis, Wellcome
Date of First Compliant Deposit: 30 April 2020
Date of Acceptance: 25 June 2020
Last Modified: 31 Jul 2020 15:40
URI: http://orca.cf.ac.uk/id/eprint/131291

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