IL-10-producing lung interstitial macrophages prevent neutrophilic asthma
IL-10-producing lung interstitial macrophages prevent neutrophilic asthma
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DOI：
10.1093/intimm/dxw012
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发表时间：
2016-10-01
影响因子：
4.4
通讯作者：
Takeda, Kiyoshi
中科院分区：
文献类型：
--
作者：
Kawano, Hideo;Kayama, Hisako;Takeda, Kiyoshi
产生 IL-10 的间质巨噬细胞可预防中性粒细胞性哮喘。炎症反应有助于宿主防御有害生物和过敏原，而免疫耐受失败可导致包括哮喘在内的慢性炎症。肺有几种先天骨髓细胞亚群。在这些亚群中，有两种类型的巨噬细胞：肺泡巨噬细胞（AM）和间质巨噬细胞（IM）。然而，与 AM 相比，IM 在肺稳态中的作用仍知之甚少。在这项研究中，我们对健康和炎症条件下的 AM 和 IM 进行了表征。肺 IM 通过以不依赖于微生物群的方式激活 TLR4/MyD88 通路，持续产生抗炎细胞因子 IL-10。除了 IM 之外，Foxp3(+) T-reg 细胞在肺中也表现出持续的 IL-10 表达，其中产生 IL-10 的 IM 比 Foxp3(+) T-reg 细胞更普遍。 IMs，而非Foxp3(+) T-reg细胞，增加了房尘螨(HDM)攻击小鼠（人类哮喘模型）中IL-10的产生。与野生型小鼠相比，HDM 攻击的 Il10(-/-) 小鼠表现出以中性粒细胞增多为特征的严重肺部病理学。此外，野生型IM的移植减少了中性粒细胞炎症、杯状细胞粘液的产生，并降低了肺IL-13和T(h)17相关的中性粒细胞激活细胞因子（例如IL-17、GM-CSF和TNF-α）的表达。这些结果共同表明，产生 IL-10 的 IM 负向调节 T(h)2 和 T(h)17 介导的炎症反应，有助于预防中性粒细胞性哮喘。
IL-10-producing interstitial macrophages prevent neutrophilic asthma.Inflammatory responses contribute to host defense against harmful organisms and allergens, whereas a failure of immune tolerance can cause chronic inflammation including asthma. The lung has several innate myeloid cell subsets. Among these subsets, there are two types of macrophages: alveolar macrophages (AMs) and interstitial macrophages (IMs). However, compared with AMs, the role of IMs in lung homeostasis remains poorly understood. In this study, we characterized AMs and IMs in healthy and inflammatory conditions. Pulmonary IMs constitutively produce the anti-inflammatory cytokine IL-10 through activation of the TLR4/MyD88 pathway in a microbiota-independent manner. In addition to IMs, Foxp3(+) T-reg cells show persistent IL-10 expression in the lung, with IL-10-producing IMs more prevalent than Foxp3(+) T-reg cells. IMs, but not Foxp3(+) T-reg cells, increased IL-10 production in house dust mite (HDM)-challenged mice, a model of human asthma. HDM-challenged Il10(-/-) mice exhibited severe lung pathology characterized by neutrophilia compared with that of wild-type mice. In addition, transplantation of wild-type IMs reduced neutrophilic inflammation, goblet cell mucus production and decreased expression of lung IL-13 and T(h)17-related neutrophil-activating cytokines such as IL-17, GM-CSF, and TNF-alpha. Together these results demonstrate that IL-10-producing IMs negatively regulate T(h)2- and T(h)17-mediated inflammatory responses, helping prevent neutrophilic asthma.