Cell
Volume 163, Issue 2, 8 October 2015, Pages 381-393
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Article
An IL-23R/IL-22 Circuit Regulates Epithelial Serum Amyloid A to Promote Local Effector Th17 Responses

https://doi.org/10.1016/j.cell.2015.08.061Get rights and content
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Highlights

  • SFB-specific Th17 cells are primed in MLN and traffic throughout the GI tract

  • IL-17A-producing Th17 cells are enriched in ileum, where SFB adheres to epithelium

  • SAA1/2 from ileal epithelial cells contributes the induction of IL-17A in Th17 cells

  • SFB-induced IL-22 production by ILC3 stimulates epithelial cells to make SAA1/2

Summary

RORγt+ Th17 cells are important for mucosal defenses but also contribute to autoimmune disease. They accumulate in the intestine in response to microbiota and produce IL-17 cytokines. Segmented filamentous bacteria (SFB) are Th17-inducing commensals that potentiate autoimmunity in mice. RORγt+ T cells were induced in mesenteric lymph nodes early after SFB colonization and distributed across different segments of the gastrointestinal tract. However, robust IL-17A production was restricted to the ileum, where SFB makes direct contact with the epithelium and induces serum amyloid A proteins 1 and 2 (SAA1/2), which promote local IL-17A expression in RORγt+ T cells. We identified an SFB-dependent role of type 3 innate lymphoid cells (ILC3), which secreted IL-22 that induced epithelial SAA production in a Stat3-dependent manner. This highlights the critical role of tissue microenvironment in activating effector functions of committed Th17 cells, which may have important implications for how these cells contribute to inflammatory disease.

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Present address: Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA