Journal article
Homeostatic PPARα Signaling Limits Inflammatory Responses to Commensal Microbiota in the Intestine
The Journal of immunology (1950), Vol.196(11), pp.4739-4749
06/01/2016
DOI: 10.4049/jimmunol.1501489
PMCID: PMC4875842
PMID: 27183583
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.
Details
- Title: Subtitle
- Homeostatic PPARα Signaling Limits Inflammatory Responses to Commensal Microbiota in the Intestine
- Creators
- Indumathi Manoharan - Cancer Center, Augusta University, Augusta, GA 30912Amol Suryawanshi - Cancer Center, Augusta University, Augusta, GA 30912Yuan Hong - Cancer Center, Augusta University, Augusta, GA 30912Punithavathi Ranganathan - Cancer Center, Augusta University, Augusta, GA 30912Arulkumaran Shanmugam - Cancer Center, Augusta University, Augusta, GA 30912Shamim Ahmad - Cancer Center, Augusta University, Augusta, GA 30912Daniel Swafford - Cancer Center, Augusta University, Augusta, GA 30912Balaji Manicassamy - Department of Microbiology, University of Chicago, Chicago, IL 60637Ganesan Ramesh - Vascular Biology Center, Augusta University, Augusta, GA 30912Pandelakis A Koni - Cancer Center, Augusta University, Augusta, GA 30912; Department of Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912; andMuthusamy Thangaraju - Cancer Center, Augusta University, Augusta, GA 30912; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912Santhakumar Manicassamy - Cancer Center, Augusta University, Augusta, GA 30912; Department of Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912; and Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912 smanicassamy@gru.edu
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.196(11), pp.4739-4749
- DOI
- 10.4049/jimmunol.1501489
- PMID
- 27183583
- PMCID
- PMC4875842
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- R01 DK097271 / NIDDK NIH HHS
- Language
- English
- Date published
- 06/01/2016
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984083279002771
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