title: IL-23-responsive innate lymphoid cells are increased in inflammatory bowel disease.
abstract: Results of experimental and genetic studies have highlighted the role of the IL-23/IL-17 axis in the pathogenesis of inflammatory bowel disease (IBD). IL-23-driven inflammation has been primarily linked to Th17 cells; however, we have recently identified a novel population of innate lymphoid cells (ILCs) in mice that produces IL-17, IL-22, and IFN-γ in response to IL-23 and mediates innate colitis. The relevance of ILC populations in human health and disease is currently poorly understood. In this study, we have analyzed the role of IL-23-responsive ILCs in the human intestine in control and IBD patients. Our results show increased expression of the Th17-associated cytokine genes IL17A and IL17F among intestinal CD3⁻ cells in IBD. IL17A and IL17F expression is restricted to CD56⁻ ILCs, whereas IL-23 induces IL22 and IL26 in the CD56⁺ ILC compartment. Furthermore, we observed a significant and selective increase in CD127⁺CD56⁻ ILCs in the inflamed intestine in Crohn's disease (CD) patients but not in ulcerative colitis patients. These results indicate that IL-23-responsive ILCs are present in the human intestine and that intestinal inflammation in CD is associated with the selective accumulation of a phenotypically distinct ILC population characterized by inflammatory cytokine expression. ILCs may contribute to intestinal inflammation through cytokine production, lymphocyte recruitment, and organization of the inflammatory tissue and may represent a novel tissue-specific target for subtypes of IBD.
authors.affiliation: Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 9DU, England, UK.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Geremia
authors.forename: Carolina V
authors.initials: CV
authors.lastname: Arancibia-Cárcamo
authors.forename: Myles P P
authors.initials: MP
authors.lastname: Fleming
authors.forename: Nigel
authors.initials: N
authors.lastname: Rust
authors.forename: Baljit
authors.initials: B
authors.lastname: Singh
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Mortensen
authors.forename: Simon P L
authors.initials: SP
authors.lastname: Travis
authors.forename: Fiona
authors.initials: F
authors.lastname: Powrie
mesh_terms: D000818:Animals; D001706:Biopsy; D017252:CD3 Complex / Q000096:biosynthesis; D019002:CD56 Antigen / Q000096:biosynthesis; D002469:Cell Separation; D003093:Colitis, Ulcerative / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis; D053759:Interleukin-23 / Q000096:biosynthesis / Q000378:metabolism*; D053699:Interleukin-7 Receptor alpha Subunit / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008214:Lymphocytes / Q000166:cytology*; D051379:Mice
chemical_list: D017252:CD3 Complex; D019002:CD56 Antigen; D016207:Cytokines; D020381:Interleukin-17; D053759:Interleukin-23; D053699:Interleukin-7 Receptor alpha Subunit