title: Interleukin-17 induces an atypical M2-like macrophage subpopulation that regulates intestinal inflammation.
abstract: Interleukin 17 (IL-17) is a pleiotropic cytokine that acts on both immune and non-immune cells and is generally implicated in inflammatory and autoimmune diseases. Although IL-17 as well as their source, mainly but not limited to Th17 cells, is also abundant in the inflamed intestine, the role of IL-17 in inflammatory bowel disease remains controversial. In the present study, by using IL-17 knockout (KO) mice, we investigated the role of IL-17 in colitis, with special focus on the macrophage subpopulations. Here we show that IL-17KO mice had increased susceptibility to DSS-induced colitis which was associated with decrease in expression of mRNAs implicated in M2 and/or wound healing macrophages, such as IL-10, IL-1 receptor antagonist, arginase 1, cyclooxygenase 2, and indoleamine 2,3-dioxygenase. Lamina propria leukocytes from inflamed colon of IL-17KO mice contained fewer CD11b+Ly6C+MHC Class II+ macrophages, which were derived, at least partly, from blood monocytes, as compared to those of WT mice. FACS-purified CD11b+ cells from WT mice, which were more abundant in Ly6C+MHC Class II+ cells, expressed increased levels of genes associated M2/wound healing macrophages and also M1/proinflammatory macrophages. Depletion of this population by topical administration of clodronate-liposome in the colon of WT mice resulted in the exacerbation of colitis. These results demonstrate that IL-17 confers protection against the development of severe colitis through the induction of an atypical M2-like macrophage subpopulation. Our findings reveal a previously unappreciated mechanism by which IL-17 exerts a protective function in colitis.
authors.affiliation: Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Nishikawa
authors.affiliation: Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Seo
authors.affiliation: Department of Cellular and Molecular Immunology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Torii
authors.affiliation: Faculty of Health Science, Suzuka University of Medical Science, Suzuka, Mie, Japan.
authors.forename: Nei
authors.initials: N
authors.lastname: Ma
authors.affiliation: Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Muraoka
authors.affiliation: Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Tawara
authors.affiliation: Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Masuya
authors.affiliation: Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Takei
authors.affiliation: Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiku
authors.affiliation: Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Katayama
authors.affiliation: Department of Cellular and Molecular Immunology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Kato
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation; D003092:Colitis / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics* / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D012720:Severity of Illness Index; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000950:Antigens, Ly; D039481:CD11b Antigen; D000949:Histocompatibility Antigens Class II; D020381:Interleukin-17; C494192:Ly-6C antigen, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D016264:Dextran Sulfate