Interleukin-17 induces an atypical M2-like macrophage subpopulation that regulates intestinal inflammation.
Interleukin-17 induces an atypical M2-like macrophage subpopulation that regulates intestinal inflammation.
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Interleukin-17 诱导非典型 M2 样巨噬细胞亚群调节肠道炎症。
DOI：
10.1371/journal.pone.0108494
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kato T
中科院分区：
文献类型：
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作者：
Nishikawa K;Seo N;Torii M;Ma N;Muraoka D;Tawara I;Masuya M;Tanaka K;Takei Y;Shiku H;Katayama N;Kato T
白细胞介素17（IL-17）是作用于免疫和非免疫细胞的多效性细胞因子，并且通常涉及炎性和自身免疫性疾病。虽然IL-17及其来源（主要但不限于Th 17细胞）在发炎的肠道中也很丰富，但IL-17在炎症性肠病中的作用仍然存在争议。在本研究中，通过使用IL-17敲除（KO）小鼠，我们研究了IL-17在结肠炎中的作用，特别关注巨噬细胞亚群。在此，我们发现IL-17 KO小鼠对DSS诱导的结肠炎的易感性增加，这与M2和/或伤口愈合巨噬细胞中涉及的mRNA表达减少有关，如IL-10，IL-1受体拮抗剂，辅酶1，环氧合酶2和吲哚胺2，3-双加氧酶。与WT小鼠相比，IL-17 KO小鼠炎症结肠的固有层白细胞含有较少的CD 11b + Ly 6C +MHC II类+巨噬细胞，其至少部分来源于血液单核细胞。来自WT小鼠的FACS纯化的CD 11b+细胞（在Ly 6C +MHC II类+细胞中更丰富）表达增加的M2/伤口愈合巨噬细胞以及M1/促炎巨噬细胞相关基因水平。通过在WT小鼠的结肠中局部施用氯膦酸盐-脂质体消耗该群体导致结肠炎恶化。这些结果表明，IL-17通过诱导非典型M2样巨噬细胞亚群来提供针对严重结肠炎发展的保护。我们的研究结果揭示了IL-17在结肠炎中发挥保护作用的一种以前未被认识的机制。
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.
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DOI：
10.4049/jimmunol.1200553
发表时间：
2012-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Schepp-Berglind J;Atkinson C;Elvington M;Qiao F;Mannon P;Tomlinson S
通讯作者：
Tomlinson S
影响因子：
29.4
作者：
Monteleone, Ivan;Rizzo, Angelamaria;Monteleone, Giovanni
通讯作者：
Monteleone, Giovanni
影响因子：
5.5
作者：
Qualls, Joseph E.;Kaplan, Alan M.;Cohen, Donald A.
通讯作者：
Cohen, Donald A.
影响因子：
2.2
作者：
PERRY, DG;MARTIN, WJ
通讯作者：
MARTIN, WJ
影响因子：
64.8
作者：
通讯作者：
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