title: Cutting Edge: IL-36 Receptor Promotes Resolution of Intestinal Damage.
abstract: IL-1 family members are central mediators of host defense. In this article, we show that the novel IL-1 family member IL-36γ was expressed during experimental colitis and human inflammatory bowel disease. Germ-free mice failed to induce IL-36γ in response to dextran sodium sulfate (DSS)-induced damage, suggesting that gut microbiota are involved in its induction. Surprisingly, IL-36R-deficient (Il1rl2(-/-)) mice exhibited defective recovery following DSS-induced damage and impaired closure of colonic mucosal biopsy wounds, which coincided with impaired neutrophil accumulation in the wound bed. Failure of Il1rl2(-/-) mice to recover from DSS-induced damage was associated with a profound reduction in IL-22 expression, particularly by colonic neutrophils. Defective recovery of Il1rl2(-/-) mice could be rescued by an aryl hydrocarbon receptor agonist, which was sufficient to restore IL-22 expression and promote full recovery from DSS-induced damage. These findings implicate the IL-36/IL-36R axis in the resolution of intestinal mucosal wounds.
authors.affiliation: Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303;
authors.forename: Oscar
authors.initials: O
authors.lastname: Medina-Contreras
authors.affiliation: Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303;
authors.forename: Akihito
authors.identifier: http://orcid.org/0000-0001-9204-1819
authors.initials: A
authors.lastname: Harusato
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322;
authors.forename: Hikaru
authors.identifier: http://orcid.org/0000-0001-6210-396X
authors.initials: H
authors.lastname: Nishio
authors.affiliation: Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303;
authors.forename: Kyle L
authors.identifier: http://orcid.org/0000-0002-9449-8879
authors.initials: KL
authors.lastname: Flannigan
authors.affiliation: Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303;
authors.forename: Vu
authors.identifier: http://orcid.org/0000-0002-9820-0443
authors.initials: V
authors.lastname: Ngo
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322;
authors.forename: Giovanna
authors.identifier: http://orcid.org/0000-0002-2722-6806
authors.initials: G
authors.lastname: Leoni
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322;
authors.forename: Philipp-Alexander
authors.identifier: http://orcid.org/0000-0003-2256-6921
authors.initials: PA
authors.lastname: Neumann
authors.affiliation: Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322;
authors.forename: Duke
authors.initials: D
authors.lastname: Geem
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322;
authors.forename: Loukia N
authors.identifier: http://orcid.org/0000-0001-9144-8449
authors.initials: LN
authors.lastname: Lili
authors.affiliation: Department of Pediatrics, University of Florida, Gainesville, FL 32607;
authors.forename: Ravisankar A
authors.identifier: http://orcid.org/0000-0001-9053-6711
authors.initials: RA
authors.lastname: Ramadas
authors.affiliation: Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303;
authors.forename: Benoit
authors.initials: B
authors.lastname: Chassaing
authors.affiliation: Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303;
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Gewirtz
authors.affiliation: Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322;
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Kohlmeier
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322; Department of Pathology, University of Michigan, Ann Arbor, MI 48109; and.
authors.forename: Charles A
authors.identifier: http://orcid.org/0000-0002-2490-7657
authors.initials: CA
authors.lastname: Parkos
authors.affiliation: Department of Inflammation Research, Amgen, Seattle, WA 98119.
authors.forename: Jennifer E
authors.identifier: http://orcid.org/0000-0002-7943-7453
authors.initials: JE
authors.lastname: Towne
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322; Department of Pathology, University of Michigan, Ann Arbor, MI 48109; and.
authors.forename: Asma
authors.initials: A
authors.lastname: Nusrat
authors.affiliation: Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303; tdenning@gsu.edu.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Denning
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000382:microbiology; D003106:Colon / Q000276:immunology / Q000293:injuries; D016264:Dextran Sulfate; D044923:Helicobacter hepaticus / Q000472:pathogenicity; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000276:immunology; D007375:Interleukin-1 / Q000096:biosynthesis*; D007378:Interleukins / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology*; D014945:Wound Healing / Q000235:genetics / Q000276:immunology*; D000097043:Interleukin-22
chemical_list: D016264:Dextran Sulfate; D007375:Interleukin-1; D007378:Interleukins; D018336:Receptors, Aryl Hydrocarbon; D018123:Receptors, Interleukin; D000097043:Interleukin-22; C569167:IL1F9 protein, mouse; C571244:interleukin-36 receptor, human