Homeostatic PPARα Signaling Limits Inflammatory Responses to Commensal Microbiota in the Intestine

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2016 May 17

PMID 27183583

Citations 45

Authors

Indumathi Manoharan

Amol Suryawanshi

Yuan Hong

Punithavathi Ranganathan

Arulkumaran Shanmugam

Shamim Ahmad

Daniel Swafford

Balaji Manicassamy

Ganesan Ramesh

Pandelakis A Koni

Muthusamy Thangaraju

Santhakumar Manicassamy

Affiliations

Soon will be listed here.

Abstract

Dietary lipids and their metabolites activate members of the peroxisome proliferative-activated receptor (PPAR) family of transcription factors and are critical for colonic health. The PPARα isoform plays a vital role in regulating inflammation in various disease settings, but its role in intestinal inflammation, commensal homeostasis, and mucosal immunity in the gut are unclear. In this study, we demonstrate that the PPARα pathway in innate immune cells orchestrates gut mucosal immunity and commensal homeostasis by regulating the expression of IL-22 and the antimicrobial peptides RegIIIβ, RegIIIγ, and calprotectin. Additionally, the PPARα pathway is critical for imparting regulatory phenotype in intestinal macrophages. PPARα deficiency in mice led to commensal dysbiosis in the gut, resulting in a microbiota-dependent increase in the expression of inflammatory cytokines and enhanced susceptibility to intestinal inflammation. Pharmacological activation of this pathway decreased the expression of inflammatory cytokines and ameliorated colonic inflammation. Taken together, these findings identify a new important innate immune function for the PPARα signaling pathway in regulating intestinal inflammation, mucosal immunity, and commensal homeostasis. Thus, the manipulation of the PPARα pathway could provide novel opportunities for enhancing mucosal immunity and treating intestinal inflammation.

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