人口
免疫系统
生物
病理
巨噬细胞
趋化因子
转录组
肺泡巨噬细胞
免疫学
肺
细胞生物学
炎症
医学
内科学
基因表达
体外
环境卫生
基因
生物化学
作者
Basak Burcu Ural,Stephen T. Yeung,Payal Damani‐Yokota,Joseph C. Devlin,Maren de Vries,Paola Vera-Licona,Tasleem Samji,Catherine M. Sawai,Geunhyo Jang,Oriana A. Perez,Quynh Mai Pham,Leigh Maher,P’ng Loke,Meike Dittmann,Boris Reizis,Kamal M. Khanna
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2020-03-13
卷期号:5 (45)
被引量:161
标识
DOI:10.1126/sciimmunol.aax8756
摘要
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 after 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.
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