Identification of a nerve-associated, lung-resident interstitial macrophage subset with distinct localization and immunoregulatory properties.
Identification of a nerve-associated, lung-resident interstitial macrophage subset with distinct localization and immunoregulatory properties.
复制标题
DOI：
10.1126/sciimmunol.aax8756
复制
发表时间：
2020-03-27
影响因子：
24.8
通讯作者：
Khanna KM
中科院分区：
文献类型：
--
作者：
Ural BB;Yeung ST;Damani-Yokota P;Devlin JC;de Vries M;Vera-Licona P;Samji T;Sawai CM;Jang G;Perez OA;Pham Q;Maher L;Loke P;Dittmann M;Reizis B;Khanna KM
组织驻留巨噬细胞是执行专门功能的细胞的多样性群体，包括维持组织稳态和组织监视。在这里，我们报告了一个CD 169+肺驻留巨噬细胞的间质亚群，它们在转录和发育上与肺泡巨噬细胞（AM）不同。它们主要位于气道周围，并发现在支气管血管束中的交感神经附近。这些神经和气道相关的巨噬细胞（NAM）是组织驻留的，卵黄囊衍生的，自我更新的，不需要CCR 2+单核细胞的发育或维持。与AM不同，NAM的发展需要CSF 1，而不是GM-CSF。大量群体和单细胞转录组分析表明，NAM不同于其他肺驻留巨噬细胞亚群，并且在稳态和炎症条件下高度表达免疫调节基因。NAM在流感感染和用TLR 3配体poly（I：C）活化后强烈增殖，并且在它们不存在的情况下，炎症反应增强，导致炎性细胞因子的过度产生和先天免疫细胞浸润。总的来说，我们的研究提供了一个独特的子集气道相关的肺巨噬细胞的功能，以维持免疫和组织的稳态的见解。肺含有CD 169+间质巨噬细胞亚群，其定位于调节肺部炎症的支气管血管树。
Tissue-resident macrophages are a diverse population of cells that perform specialized functions including sustaining tissue homeostasis and tissue surveillance. Here we report an interstitial subset of CD169+ lung-resident macrophages that are transcriptionally and developmentally distinct from alveolar macrophages (AMs). They are primarily localized around the airways and are found in close proximity to the sympathetic nerves in the bronchovascular bundle. These nerve- and airway-associated macrophages (NAMs) are tissue-resident, yolk sac-derived, self-renewing, and do not require CCR2+ monocytes for development or maintenance. Unlike AMs, the development of NAMs requires CSF1, but not GM-CSF. Bulk population and single cell transcriptome analysis indicated that NAMs are distinct from other lung resident macrophage subsets and highly express immunoregulatory genes under steady state and inflammatory conditions. NAMs proliferated robustly following influenza infection and activation with the TLR3 ligand poly(I:C), and in their absence, the inflammatory response was augmented resulting in excessive production of inflammatory cytokines and innate immune cell infiltration. Overall, our study provides insights into a distinct subset of airway-associated pulmonary macrophages that function to maintain immune and tissue homeostasis. The lungs contain a CD169+ interstitial macrophage subset localized to the bronchovascular tree that regulates lung inflammation.
登录
查看更多内容
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
64.5
作者：
Gosselin D;Link VM;Romanoski CE;Fonseca GJ;Eichenfield DZ;Spann NJ;Stender JD;Chun HB;Garner H;Geissmann F;Glass CK
通讯作者：
Glass CK
影响因子：
16.6
作者：
Asano K;Takahashi N;Ushiki M;Monya M;Aihara F;Kuboki E;Moriyama S;Iida M;Kitamura H;Qiu CH;Watanabe T;Tanaka M
通讯作者：
Tanaka M
影响因子：
30.5
作者：
通讯作者：
--