RXRα Regulates the Development of Resident Tissue Macrophages.
RXRα Regulates the Development of Resident Tissue Macrophages.
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DOI：
10.4049/immunohorizons.2200019
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发表时间：
2022-06-22
期刊：
影响因子：
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通讯作者：
Jain, Nitya
中科院分区：
文献类型：
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作者：
Philpott, Jordan;Kazimierczyk, Simon;Korgaonkar, Parimal;Bordt, Evan;Zois, Jaclyn;Vasudevan, Chithirachelvi;Meng, Di;Bhatia, Ishan;Lu, Naifang;Jimena, Brittany;Porter, Caryn;Cherayil, Bobby J;Jain, Nitya
驻留组织巨噬细胞（RTMs）从出生前播种组织的胚胎祖细胞的不同波发展而来。组织特异性信号驱动分化程序，导致RTM子集的功能专业化。调控RTMs发展的遗传程序尚未完全了解，使其在成年期得以维持的机制也是如此。在这项研究中，我们发现，配体激活的核激素受体，类维生素A X受体（RXR）α，是小鼠RTM发展的关键调节因子。造血前体中RXRα的缺失严重减少了成人组织中的RTM群体，包括脾、腹膜腔、肺和肝。这种缺陷可以追溯到胚胎期，在造血谱系中缺乏RXRα的小鼠的卵黄囊和胎肝巨噬细胞数量大大减少，这种缺乏持续到出生后不久。
Resident tissue macrophages (RTMs) develop from distinct waves of embryonic progenitor cells that seed tissues before birth. Tissue-specific signals drive a differentiation program that leads to the functional specialization of RTM subsets. Genetic programs that regulate the development of RTMs are incompletely understood, as are the mechanisms that enable their maintenance in adulthood. In this study, we show that the ligand-activated nuclear hormone receptor, retinoid X receptor (RXR)α, is a key regulator of murine RTM development. Deletion of RXRα in hematopoietic precursors severely curtailed RTM populations in adult tissues, including the spleen, peritoneal cavity, lung, and liver. The deficiency could be traced to the embryonic period, and mice lacking RXRα in hematopoietic lineages had greatly reduced numbers of yolk sac and fetal liver macrophages, a paucity that persisted into the immediate postnatal period.