Homeostatic PPARα Signaling Limits Inflammatory Responses to Commensal Microbiota in the Intestine.
Homeostatic PPARα Signaling Limits Inflammatory Responses to Commensal Microbiota in the Intestine.
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DOI：
10.4049/jimmunol.1501489
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发表时间：
2016-06-01
期刊：
影响因子：
--
通讯作者：
Manicassamy S
中科院分区：
文献类型：
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作者：
Manoharan I;Suryawanshi A;Hong Y;Ranganathan P;Shanmugam A;Ahmad S;Swafford D;Manicassamy B;Ramesh G;Koni PA;Thangaraju M;Manicassamy S
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. Here, 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 anti-microbial peptides RegIIIβ, RegIIIγ and calprotectin. In addition, the PPARα pathway is critical for imparting regulatory phenotype in intestinal macrophages. PPARα deficiency in mice resulted in commensal dysbiosis in the gut resulting in 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. 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.
