The lung microenvironment shapes a dysfunctiona response of alveolar macrophages in aging
The lung microenvironment shapes a dysfunctiona response of alveolar macrophages in aging
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DOI：
10.1172/jci140299
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发表时间：
2021-02-15
影响因子：
15.9
通讯作者：
Budinger, G. R. Scott
中科院分区：
文献类型：
--
作者：
McQuattie-Pimentel, Alexandra C.;Ren, Ziyou;Budinger, G. R. Scott
肺泡巨噬细胞协调对病毒感染的反应。这些细胞中与肺炎相关的变化可能是老年患者肺炎严重程度不同的基础。我们对单细胞RNA-Seq数据进行了综合分析，揭示了人类和小鼠肺泡巨噬细胞转录组的同质年龄相关变化。使用遗传谱系追踪与序贯损伤，异时过继转移，和联体，我们发现，肺微环境驱动的年龄相关的阻力肺泡巨噬细胞增殖，持续在甲型流感病毒感染。配体-受体对分析将这些变化定位于细胞外基质，其中透明质酸在老年动物中增加，并改变骨髓源性巨噬细胞对粒细胞巨噬细胞集落刺激因子（GM-CSF）的增殖反应。我们的研究结果表明，针对老化的肺微环境的策略将是必要的，以恢复肺泡巨噬细胞功能的老化。
Alveolar macrophages orchestrate the response to viral infections. Age-related changes in these cells may underlie the differential severity of pneumonia in older patients. We performed an integrated analysis of single-cell RNA-Seq data that revealed homogenous age-related changes in the alveolar macrophage transcriptome in humans and mice. Using genetic lineage tracing with sequential injury, heterochronic adoptive transfer, and parabiosis, we found that the lung microenvironment drove an age-related resistance of alveolar macrophages to proliferation that persisted during influenza A viral infection. Ligand-receptor pair analysis localized these changes to the extracellular matrix, where hyaluronan was increased in aged animals and altered the proliferative response of bone marrow-derived macrophages to granulocyte macrophage colony-stimulating factor (GM-CSF). Our findings suggest that strategies targeting the aging lung microenvironment will be necessary to restore alveolar macrophage function in aging.