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Interleukin-17 Induces an Atypical M2-Like Macrophage Subpopulation That Regulates Intestinal Inflammation
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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177893/ https://www.ncbi.nlm.nih.gov/pubmed/25254662 http://dx.doi.org/10.1371/journal.pone.0108494 |
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author | Nishikawa, Kenichiro Seo, Naohiro Torii, Mie Ma, Nei Muraoka, Daisuke Tawara, Isao Masuya, Masahiro Tanaka, Kyosuke Takei, Yoshiyuki Shiku, Hiroshi Katayama, Naoyuki Kato, Takuma |
author_facet | Nishikawa, Kenichiro Seo, Naohiro Torii, Mie Ma, Nei Muraoka, Daisuke Tawara, Isao Masuya, Masahiro Tanaka, Kyosuke Takei, Yoshiyuki Shiku, Hiroshi Katayama, Naoyuki Kato, Takuma |
author_sort | Nishikawa, Kenichiro |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4177893 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-41778932014-10-02 Interleukin-17 Induces an Atypical M2-Like Macrophage Subpopulation That Regulates Intestinal Inflammation Nishikawa, Kenichiro Seo, Naohiro Torii, Mie Ma, Nei Muraoka, Daisuke Tawara, Isao Masuya, Masahiro Tanaka, Kyosuke Takei, Yoshiyuki Shiku, Hiroshi Katayama, Naoyuki Kato, Takuma PLoS One Research Article 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. Public Library of Science 2014-09-25 /pmc/articles/PMC4177893/ /pubmed/25254662 http://dx.doi.org/10.1371/journal.pone.0108494 Text en © 2014 Nishikawa et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Nishikawa, Kenichiro Seo, Naohiro Torii, Mie Ma, Nei Muraoka, Daisuke Tawara, Isao Masuya, Masahiro Tanaka, Kyosuke Takei, Yoshiyuki Shiku, Hiroshi Katayama, Naoyuki Kato, Takuma Interleukin-17 Induces an Atypical M2-Like Macrophage Subpopulation That Regulates Intestinal Inflammation |
title | Interleukin-17 Induces an Atypical M2-Like Macrophage Subpopulation That Regulates Intestinal Inflammation |
title_full | Interleukin-17 Induces an Atypical M2-Like Macrophage Subpopulation That Regulates Intestinal Inflammation |
title_fullStr | Interleukin-17 Induces an Atypical M2-Like Macrophage Subpopulation That Regulates Intestinal Inflammation |
title_full_unstemmed | Interleukin-17 Induces an Atypical M2-Like Macrophage Subpopulation That Regulates Intestinal Inflammation |
title_short | Interleukin-17 Induces an Atypical M2-Like Macrophage Subpopulation That Regulates Intestinal Inflammation |
title_sort | interleukin-17 induces an atypical m2-like macrophage subpopulation that regulates intestinal inflammation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177893/ https://www.ncbi.nlm.nih.gov/pubmed/25254662 http://dx.doi.org/10.1371/journal.pone.0108494 |
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