Mucosal Immunology and Biology Research Center, Mass General Hospital for Children, Charlestown, MA.
Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston MA.
Immunohorizons. 2022 Jun 22;6(6):366-372. doi: 10.4049/immunohorizons.2200019.
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.
驻留组织巨噬细胞（RTMs）由在出生前播种组织的不同胚胎祖细胞波发育而来。组织特异性信号驱动分化程序，导致 RTM 亚群的功能特化。调控 RTMs 发育的遗传程序尚未完全了解，使它们在成年期得以维持的机制也尚不清楚。在这项研究中，我们表明配体激活的核激素受体，视黄酸 X 受体（RXR）α，是调控小鼠 RTMs 发育的关键调节因子。在造血前体中删除 RXRα 严重限制了成年组织中的 RTM 群体，包括脾脏、腹腔、肺和肝脏。这种缺陷可以追溯到胚胎期，并且造血谱系中缺乏 RXRα 的小鼠卵黄囊和胎肝巨噬细胞数量大大减少，这种不足一直持续到出生后的早期阶段。
