title: IL-36α expression is elevated in ulcerative colitis and promotes colonic inflammation.
abstract: A role for the IL-36 family of cytokines has been identified in the pathogenesis of psoriasis. Although significant mechanistic overlap can exist between psoriasis and inflammatory bowel disease (IBD), to date there have been no reports investigating the IL-36 family in gastrointestinal inflammation. Here we demonstrate that expression levels of IL-36α are specifically elevated in the colonic mucosa of ulcerative colitis patients. This elevated expression is mirrored in the inflamed colonic mucosa of mice, wherein IL-36 receptor deficiency confirmed this pathway as a mediator of mucosal inflammation. Il36r-/- mice exhibited reduced disease severity in an acute DSS-induced model of colitis in association with decreased innate inflammatory cell infiltration to the colon lamina propria. Consistent with these data, infection with the enteropathogenic bacteria Citrobacter rodentium, resulted in reduced innate inflammatory cell recruitment and increased bacterial colonization in the colons of il36r-/- mice. Il36r-/- mice also exhibited altered T helper cell responses in this model, with enhanced Th17 and reduced Th1 responses, demonstrating that IL-36R signaling also regulates intestinal mucosal T-cell responses. These data identify a novel role for IL-36 signaling in colonic inflammation and indicate that the IL-36R pathway may represent a novel target for therapeutic intervention in IBD.
authors.affiliation: Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland.|National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: S E
authors.initials: SE
authors.lastname: Russell
authors.affiliation: Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland.|National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: R M
authors.initials: RM
authors.lastname: Horan
authors.affiliation: Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland.|National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: A M
authors.initials: AM
authors.lastname: Stefanska
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: A
authors.initials: A
authors.lastname: Carey
authors.affiliation: Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland.|National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: G
authors.initials: G
authors.lastname: Leon
authors.affiliation: APC Microbiome Institute, University College Cork, National University of Ireland, Cork, Ireland.
authors.forename: M
authors.initials: M
authors.lastname: Aguilera
authors.affiliation: APC Microbiome Institute, University College Cork, National University of Ireland, Cork, Ireland.
authors.forename: D
authors.initials: D
authors.lastname: Statovci
authors.affiliation: Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland.|National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: T
authors.initials: T
authors.lastname: Moran
authors.affiliation: Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland.|National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: P G
authors.initials: PG
authors.lastname: Fallon
authors.affiliation: APC Microbiome Institute, University College Cork, National University of Ireland, Cork, Ireland.
authors.forename: F
authors.initials: F
authors.lastname: Shanahan
authors.affiliation: Department of Pathology, University College Cork, Cork, Ireland.
authors.forename: E K
authors.initials: EK
authors.lastname: Brint
authors.affiliation: APC Microbiome Institute, University College Cork, National University of Ireland, Cork, Ireland.
authors.forename: S
authors.initials: S
authors.lastname: Melgar
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.|Academic Centre for Paediatric Research, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: S
authors.initials: S
authors.lastname: Hussey
authors.affiliation: Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland.|National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: P T
authors.initials: PT
authors.lastname: Walsh
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002648:Child; D044082:Citrobacter rodentium / Q000254:growth & development / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000473:pathology; D016264:Dextran Sulfate; D004756:Enterobacteriaceae Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D018928:Immunity, Mucosal; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology*; D017472:Receptors, Interleukin-1 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D016264:Dextran Sulfate; D007375:Interleukin-1; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1; C572887:interleukin 36, human; C571244:interleukin-36 receptor, human; C569500:Il1rl2 protein, mouse
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