title: Intestinal Interleukin-17 Receptor Signaling Mediates Reciprocal Control of the Gut Microbiota and Autoimmune Inflammation.
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.
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA 15224, USA.
authors.forename: Pawan
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA 15224, USA.
authors.forename: Leticia
authors.initials: L
authors.lastname: Monin
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA 15224, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Castillo
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA 15224, USA.
authors.forename: Waleed
authors.initials: W
authors.lastname: Elsegeiny
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA 15224, USA.
authors.forename: William
authors.initials: W
authors.lastname: Horne
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA 15224, USA.
authors.forename: Taylor
authors.initials: T
authors.lastname: Eddens
authors.affiliation: Department of Civil and Environmental Engineering, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Vikram
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA 15224, USA.
authors.forename: Misty
authors.initials: M
authors.lastname: Good
authors.affiliation: Division of Pediatric Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Alexi A
authors.initials: AA
authors.lastname: Schoenborn
authors.affiliation: Department of Civil and Environmental Engineering, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Bibby
authors.affiliation: Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Montelaro
authors.affiliation: Center for Immunology & Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Metzger
authors.affiliation: Division of Pediatric Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Ajay S
authors.initials: AS
authors.lastname: Gulati
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, PA 15224, USA. Electronic address: jay.kolls@chp.edu.
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
mesh_terms: D000818:Animals; D064806:Dysbiosis / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D016908:Gram-Positive Bacterial Infections / Q000276:immunology*; D016936:Gram-Positive Endospore-Forming Bacteria / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D018928:Immunity, Mucosal / Q000235:genetics; D020381:Interleukin-17 / Q000378:metabolism; D007422:Intestines / Q000382:microbiology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064307:Microbiota; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000074624:NADPH Oxidase 1; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D058504:Th17 Cells / Q000276:immunology* / Q000382:microbiology; D023084:alpha-Defensins / Q000235:genetics / Q000378:metabolism
chemical_list: D020381:Interleukin-17; C450519:Oscar protein, mouse; D011956:Receptors, Cell Surface; D053722:Receptors, Interleukin-17; D023084:alpha-Defensins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; C000614711:NOX1 protein, mouse