Cutting Edge: Intestinal IL-17A Receptor Signaling Specifically Regulates High-Fat Diet-Mediated, Microbiota-Driven Metabolic Disorders

J Immunol. 2021 Sep 20:ji2000986. doi: 10.4049/jimmunol.2000986. Online ahead of print.ABSTRACTPrevious studies indicate that IL-17A plays an important role in mediating the intestinal microbiota and systemic metabolic functions. However, it is not known where IL-17RA signaling occurs to mediate these effects. To investigate this question, we used intestinal epithelial-specific (Il17raIEC ) and liver-specific (Il17raLiver ) IL-17RA knockout mice as well as littermate control mice. Our results indicate that intestinal IL-17RA signaling helps mediate systemic metabolic functions upon exposure to prolonged high-fat diet. Il17raIEC mice display impaired glucose metabolism, altered hormone and adipokine levels, increased visceral adiposity, and greater hepatic lipid deposition when compared with their littermate controls. We show that IL-17RA-driven changes in microbiota composition are responsible for regulating systemic glucose metabolism. Altogether, our data elucidate the importance of intestinal IL-17RA signaling in regulating high-fat diet-mediated systemic glucose and lipid metabolism.PMID:34544802 | DOI:10.4049/jimmunol.2000986
Source: Journal of Immunology - Category: Allergy & Immunology Authors: Source Type: research