2. Academic Validation
  3. Innate lymphoid cells originate from fetal liver-derived tissue-resident progenitors

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

  • Sci Immunol. 2025 Jul 11;10(109):eadu7962. doi: 10.1126/sciimmunol.adu7962.
Xianwei Wang 1,  Jiarui Li 1,  Lucas Rebuffet 2,  Ming Cheng 1,  Boqun Bao 1,  Yawen Chen 1,  Xiaodong Zheng 1,  Yongyan Chen 1,  Haoyu Sun 3 4 5,  Rui Sun 1,  Eric Vivier 2 6 7 8 9,  Hui Peng 1,  Zhigang Tian 1
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
  • 4 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
  • 5 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • 6 Innate Pharma Research Laboratories, Innate Pharma, Marseille, France.
  • 7 APHM, Hôpital de la Timone, Marseille-Immunopole Profiling Platform, Marseille, France.
  • 8 Paris-Saclay Cancer Cluster, Villejuif, France.
  • 9 Université Paris-Saclay, Gustave Roussy, INSERM, Prédicteurs moléculaires et nouvelles cibles en oncologie, Villejuif, France.
PMID: 40644510 DOI: 10.1126/sciimmunol.adu7962
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.

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