Innate Immunity, German Rheumatism Research Center (DRFZ), Leibniz Association, Berlin 10117, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectious Diseases, Rheumatology, Berlin 10117, Germany.
Innate Immunity, German Rheumatism Research Center (DRFZ), Leibniz Association, Berlin 10117, Germany.
Immunity. 2021 Oct 12;54(10):2417-2432.e5. doi: 10.1016/j.immuni.2021.07.019. Epub 2021 Aug 27.
Innate lymphoid cells (ILCs) are critical effectors of innate immunity and inflammation, whose development and activation pathways make for attractive therapeutic targets. However, human ILC generation has not been systematically explored, and previous in vitro investigations relied on the analysis of few markers or cytokines, which are suboptimal to assign lineage identity. Here, we developed a platform that reliably generated human ILC lineages from CD34 hematopoietic progenitors derived from cord blood and bone marrow. We showed that one culture condition is insufficient to generate all ILC subsets, and instead, distinct combination of cytokines and Notch signaling are essential. The identity of natural killer (NK)/ILC1s, ILC2s, and ILC3s generated in vitro was validated by protein expression, functional assays, and both global and single-cell transcriptome analysis, recapitulating the signatures and functions of their ex vivo ILC counterparts. These data represent a resource to aid in clarifying ILC biology and differentiation.
先天淋巴细胞（ILCs）是先天免疫和炎症的关键效应细胞，其发育和激活途径是有吸引力的治疗靶点。然而，人类 ILC 的产生尚未得到系统的研究，以前的体外研究依赖于少数标记物或细胞因子的分析，这不足以确定谱系身份。在这里，我们开发了一种平台，能够从脐带血和骨髓来源的 CD34 造血祖细胞中可靠地产生人类 ILC 谱系。我们表明，一种培养条件不足以产生所有的 ILC 亚群，相反，不同的细胞因子和 Notch 信号组合是必不可少的。体外生成的自然杀伤（NK）/ILC1、ILC2 和 ILC3 的特性通过蛋白表达、功能测定以及全基因组和单细胞转录组分析得到验证，重现了它们在体 ILC 对应物的特征和功能。这些数据代表了一个资源，有助于阐明 ILC 生物学和分化。
