Diverse homeostatic and immunomodulatory roles of immune cells in the developing mouse lung at single cell resolution
Diverse homeostatic and immunomodulatory roles of immune cells in the developing mouse lung at single cell resolution
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DOI：
10.7554/elife.56890
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发表时间：
2020-06-02
期刊：
影响因子：
7.7
通讯作者：
Alvira, Cristina M.
中科院分区：
文献类型：
--
作者：
Domingo-Gonzalez, Racquel;Zanini, Fabio;Alvira, Cristina M.
在出生时，肺从无病原体的缺氧环境迅速转变为富含病原体的有节奏扩张的气液界面。虽然许多研究都集中在成人肺，围产期肺仍然没有探索。在这里，我们展示了出生后早期发育期间小鼠肺部免疫区室的图谱。我们发现，晚期胚胎肺主要是由专门的增殖巨噬细胞与发展中的脉管系统的一个令人惊讶的物理相互作用。这些巨噬细胞在出生后消失，并被巨噬细胞亚型、树突细胞、粒细胞和淋巴细胞的动态混合物所取代。巨噬细胞多样性的详细表征揭示了不同亚群在出生后发育中的协调，以填补组织重塑，血管生成和免疫中的特定功能。这些数据拓宽了免疫细胞在发育中的肺中的假定作用，并为理解外部损伤如何在肺快速生长和脆弱性增加期间改变免疫细胞表型提供了框架。
At birth, the lungs rapidly transition from a pathogen-free, hypoxic environment to a pathogen-rich, rhythmically distended air-liquid interface. Although many studies have focused on the adult lung, the perinatal lung remains unexplored. Here, we present an atlas of the murine lung immune compartment during early postnatal development. We show that the late embryonic lung is dominated by specialized proliferative macrophages with a surprising physical interaction with the developing vasculature. These macrophages disappear after birth and are replaced by a dynamic mixture of macrophage subtypes, dendritic cells, granulocytes, and lymphocytes. Detailed characterization of macrophage diversity revealed an orchestration of distinct subpopulations across postnatal development to fill context-specific functions in tissue remodeling, angiogenesis, and immunity. These data both broaden the putative roles for immune cells in the developing lung and provide a framework for understanding how external insults alter immune cell phenotype during a period of rapid lung growth and heightened vulnerability.