Intestinal Interleukin-17 Receptor Signaling Mediates Reciprocal Control of the Gut Microbiota and Autoimmune Inflammation

Pawan Kumar, Leticia Monin, Patricia Castillo, Waleed Elsegeiny, William Horne, Taylor Eddens, Amit Vikram, Misty Good, Alexi A. Schoenborn, Kyle Bibby, Ronald C. Montelaro, Dennis W. Metzger, Ajay S. Gulati, Jay K. Kolls

Research output: Contribution to journalArticlepeer-review

140 Scopus citations

Abstract

Interleukin-17 (IL-17) and IL-17 receptor (IL-17R) signaling are essential for regulating mucosal host defense against many invading pathogens. Commensal bacteria, especially segmented filamentous bacteria (SFB), are a crucial factor that drives T helper 17 (Th17) cell development in the gastrointestinal tract. In this study, we demonstrate that Th17 cells controlled SFB burden. Disruption of IL-17R signaling in the enteric epithelium resulted in SFB dysbiosis due to reduced expression of α-defensins, Pigr, and Nox1. When subjected to experimental autoimmune encephalomyelitis, IL-17R-signaling-deficient mice demonstrated earlier disease onset and worsened severity that was associated with increased intestinal Csf2 expression and elevated systemic GM-CSF cytokine concentrations. Conditional deletion of IL-17R in the enteric epithelium demonstrated that there was a reciprocal relationship between the gut microbiota and enteric IL-17R signaling that controlled dysbiosis, constrained Th17 cell development, and regulated the susceptibility to autoimmune inflammation.

Original languageEnglish
Pages (from-to)659-671
Number of pages13
JournalImmunity
Volume44
Issue number3
DOIs
StatePublished - Mar 15 2016

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