固有淋巴细胞起源于胎儿肝脏来源的组织驻留祖细胞。

Innate lymphoid cells originate from fetal liver-derived tissue-resident progenitors.

作者信息

Wang Xianwei, Li Jiarui, Rebuffet Lucas, Cheng Ming, Bao Boqun, Chen Yawen, Zheng Xiaodong, Chen Yongyan, Sun Haoyu, Sun Rui, Vivier Eric, Peng Hui, Tian Zhigang

机构信息

State Key Laboratory of Immune Response and Immunotherapy, the Institute of Immunology, Biomedical Sciences and Health Laboratory of Anhui Province, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.

Aix Marseille Université, CNRS (Centre National de la Recherche Scientifique), INSERM (Institut National de la Santé et de la Recherche Médicale), Centre d'Immunologie de Marseille-Luminy, Marseille, France.

出版信息

Sci Immunol. 2025 Jul 11;10(109):eadu7962. doi: 10.1126/sciimmunol.adu7962.

DOI:10.1126/sciimmunol.adu7962

PMID:40644510

Abstract

Committed progenitors with innate lymphoid cell (ILC) developmental potential are present in the fetus and bone marrow (BM). However, how fetal and BM hematopoiesis temporally and spatially contribute to ILC pools remains unclear. Here, we elucidated the distinct origins and developmental pathways of extramedullary and intramedullary ILCs in mice during ontogeny. ILC-restricted hematopoiesis is initiated in the fetal liver (FL), and then FL-derived PD-1 ILC precursors (ILCPs) seed fetal lung and intestine. Organ niches determine the commitment of ILCPs to downstream precursors, including bipotent ILC1-ILC3 precursors (ILC1/3Ps), which preferentially reside in the liver and intestine, and ILC2 precursors (ILC2Ps), which are found predominantly in the lung. These precursors persist in adulthood and contribute to local ILC pools in a BM-independent manner. In contrast, intramedullary ILC2Ps and ILC2s rely on BM hematopoiesis. Thus, our study demonstrates that extramedullary and intramedullary ILCs have different origins and provides a comprehensive framework for ILC developmental dynamics.

摘要

具有先天淋巴细胞（ILC）发育潜能的定向祖细胞存在于胎儿和骨髓（BM）中。然而，胎儿和骨髓造血在时间和空间上如何对ILC库产生影响仍不清楚。在这里，我们阐明了小鼠个体发育过程中外髓和内髓ILC的不同起源和发育途径。ILC特异性造血在胎儿肝脏（FL）中启动，然后源自FL的PD-1 ILC前体（ILCP）定植于胎儿肺和肠道。器官微环境决定了ILCP向下游前体的分化，包括双能ILC1-ILC3前体（ILC1/3P），其优先存在于肝脏和肠道中，以及ILC2前体（ILC2P），其主要存在于肺中。这些前体在成年期持续存在，并以不依赖骨髓的方式对局部ILC库产生贡献。相比之下，髓内ILC2P和ILC2依赖于骨髓造血。因此，我们的研究表明外髓和内髓ILC有不同的起源，并为ILC发育动力学提供了一个全面的框架。