1. Interleukin-17 induces an atypical M2-like macrophage subpopulation that regulates intestinal inflammation.
- Author
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Nishikawa K, Seo N, Torii M, Ma N, Muraoka D, Tawara I, Masuya M, Tanaka K, Takei Y, Shiku H, Katayama N, and Kato T
- Subjects
- Animals, Antigens, Ly metabolism, CD11b Antigen metabolism, Cell Count, Cell Differentiation, Colitis chemically induced, Colitis metabolism, Colitis pathology, Dextran Sulfate adverse effects, Disease Models, Animal, Gene Expression Profiling, Gene Expression Regulation, Histocompatibility Antigens Class II immunology, Histocompatibility Antigens Class II metabolism, Mice, Mice, Knockout, Monocytes cytology, Monocytes immunology, Monocytes metabolism, Phenotype, RNA, Messenger genetics, Severity of Illness Index, Transcription Factors genetics, Transcription Factors metabolism, Colitis genetics, Colitis immunology, Interleukin-17 genetics, Interleukin-17 metabolism, Macrophages immunology, Macrophages metabolism
- 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.
- Published
- 2014
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