Identification and distribution of developing innate lymphoid cells in the fetal mouse intestine.
Identification and distribution of developing innate lymphoid cells in the fetal mouse intestine.
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胎儿淋巴组织诱导 (LTi) 细胞是淋巴结和派尔氏淋巴结 (PP) 器官发生所必需的，但这些特化的第 3 组先天淋巴细胞 (ILC3) 在何处发育仍不清楚。在这里，我们鉴定了肝外精氨酸酶-1+、Id2+胎儿ILC前体，它们表达过渡发育表型（ftILCP）并在体外分化为ILC1、ILC2和ILC3。这些细胞在胚胎第 (E) 13.5 天时就在肠道中繁殖，并且在 PP 器官发生之前 (E14.5-E15) 广泛分散在近端肠道中，与 PP 首次发育的区域相关。在 E16.5，PP 发育开始后，ftILCP 以淋巴毒素-α 依赖性方式在 PP 原基处积累。因此，ftILCP 在 PP 发育过程中驻留在肠道中，在基质细胞激活后它们在 PP 原基处聚集，并成为 ILC 群体的局部来源。
Fetal lymphoid tissue inducer (LTi) cells are required for lymph node and Peyer’s patch (PP) organogenesis, but where these specialized group 3 innate lymphoid cells (ILC3s) develop remains unclear. Here, we identify extrahepatic arginase-1+, Id2+ fetal ILC precursors that express a transitional developmental phenotype (ftILCPs) and differentiate into ILC1s, ILC2s, and ILC3s in vitro. These cells populate the intestine by embryonic day (E) 13.5, and prior to PP organogenesis (E14.5-E15) are broadly dispersed in the proximal gut, correlating with regions where PPs first develop. At E16.5, after PP development begins, ftILCPs accumulate at PP anlagen in a lymphotoxin-α-dependent manner. Thus, ftILCPs reside in the intestine during PP development, where they aggregate at PP anlagen after stromal cell activation and become a localized source of ILC populations.