Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Institute of Immunology, University of Science and Technology of China, Hefei, China.
Science. 2021 Mar 26;371(6536). doi: 10.1126/science.aba4177.
The pathways that lead to the development of tissue-resident lymphocytes, including liver type 1 innate lymphoid cells (ILC1s), remain unclear. We show here that the adult mouse liver contains LinSca-1Mac-1 hematopoietic stem cells derived from the fetal liver. This population includes LinCD122CD49a progenitors that can generate liver ILC1s but not conventional natural killer cells. Interferon-γ (IFN-γ) production by the liver ILC1s themselves promotes the development of these cells in situ, through effects on their IFN-γR liver progenitors. Thus, an IFN-γ-dependent loop drives liver ILC1 development in situ, highlighting the contribution of extramedullary hematopoiesis to regional immune composition within the liver.
导致组织驻留淋巴细胞(包括肝脏 1 型先天淋巴细胞(ILC1))发展的途径仍不清楚。我们在这里表明,成年小鼠肝脏中含有来自胎儿肝脏的 LinSca-1Mac-1 造血干细胞。该群体包括 LinCD122CD49a 祖细胞,可生成肝脏 ILC1,但不能生成常规自然杀伤细胞。肝脏 ILC1 本身产生的干扰素-γ(IFN-γ)通过对其 IFN-γR 肝祖细胞的作用,促进这些细胞在原位的发育。因此,IFN-γ 依赖性循环驱动肝脏 ILC1 在原位的发育,突出了骨髓外造血对肝脏内区域免疫组成的贡献。