The perinatal period is a critical window for distribution of innate tissue-resident immune cells within developing organs. Despite epidemiologic evidence implicating the early-life environment in the risk for allergy, temporally controlled lineage tracing of group 2 innate lymphoid cells (ILC2s) during this period remains unstudied. Using complementary fate-mapping approaches and reporters for ILC2 activation, we show that ILC2s appeared in multiple organs during late gestation like tissue macrophages, but, unlike the latter, a majority of peripheral ILC2 pools were generated de novo during the postnatal window. This period was accompanied by systemic ILC2 priming and acquisition of tissue-specific transcriptomes. Although perinatal ILC2s were variably replaced across tissues with age, the dramatic increases in tissue ILC2s following helminth infection were mediated through local expansion independent of de novo generation by bone marrow hematopoiesis. We provide comprehensive temporally controlled fate mapping of an innate lymphocyte subset with notable nuances as compared to tissue macrophage ontogeny.

围产期是先天组织驻留免疫细胞在发育器官内分布的关键窗口。尽管流行病学证据表明早期生活环境与过敏风险有关，但这一时期第 2 组先天淋巴细胞 (ILC2) 的时间控制谱系追踪仍未得到研究。使用互补的命运图谱方法和 ILC2 激活报告基因，我们发现 ILC2 在妊娠晚期出现在多个器官中，如组织巨噬细胞，但与后者不同的是，大多数外周 ILC2 池是在出生后窗口期从头生成的。这一时期伴随着系统性 ILC2 启动和组织特异性转录组的获取。尽管围产期ILC2随着年龄的增长在不同组织中被不同程度地替换，但蠕虫感染后组织ILC2的急剧增加是通过局部扩张介导的，与骨髓造血的从头生成无关。我们提供了先天淋巴细胞子集的全面的时间控制命运图谱，与组织巨噬细胞个体发育相比具有显着的细微差别。