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: Kenichiro Nishikawa, Naohiro Seo, Mie Torii, Nei Ma, Daisuke Muraoka, Isao Tawara, Masahiro Masuya, Kyosuke Tanaka, Yoshiyuki Takei, Hiroshi Shiku, Naoyuki Katayama, Takuma Kato
• Journal: PloS one (PLoS One) Vol. 9 Issue 9 Pg. e108494 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25254662 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Ly
• CD11b Antigen
• Histocompatibility Antigens Class II
• Interleukin-17
• Ly-6C antigen, mouse
• RNA, Messenger
• Transcription Factors
• Dextran Sulfate

Topics

• Animals
• Antigens, Ly (metabolism)
• CD11b Antigen (metabolism)
• Cell Count
• Cell Differentiation
• Colitis (chemically induced, genetics, immunology, metabolism, pathology)
• Dextran Sulfate (adverse effects)
• Disease Models, Animal
• Gene Expression Profiling
• Gene Expression Regulation
• Histocompatibility Antigens Class II (immunology, metabolism)
• Interleukin-17 (genetics, metabolism)
• Macrophages (immunology, metabolism)
• Mice
• Mice, Knockout
• Monocytes (cytology, immunology, metabolism)
• Phenotype
• RNA, Messenger (genetics)
• Severity of Illness Index
• Transcription Factors (genetics, metabolism)