Department of Internal Medicine I, University of Bonn, 53127 Bonn, Germany; German Center for Infection Research (DZIF), 53127 Bonn, Germany.
Medical Scientist Training Program, The Ohio State University, Columbus, OH 43210, USA; Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH 43210, USA.
Cell Rep. 2023 Jan 31;42(1):111937. doi: 10.1016/j.celrep.2022.111937. Epub 2023 Jan 1.
Group 1 innate lymphoid cells (ILCs) comprise a heterogeneous family of cytotoxic natural killer (NK) cells and ILC1s. We identify a population of "liver-type" ILC1s with transcriptional, phenotypic, and functional features distinct from those of conventional and liver-resident NK cells as well as from other previously described human ILC1 subsets. LT-ILC1s are CD49aCD94CD200R1, express the transcription factor T-BET, and do not express the activating receptor NKp80 or the transcription factor EOMES. Similar to NK cells, liver-type ILC1s produce IFN-γ, TNF-α, and GM-CSF; however, liver-type ILC1s also produce IL-2 and lack perforin and granzyme-B. Liver-type ILC1s are expanded in cirrhotic liver tissues, and they can be produced from blood-derived ILC precursors in vitro in the presence of TGF-β1 and liver sinusoidal endothelial cells. Cells with similar signature and function can also be found in tonsil and intestinal tissues. Collectively, our study identifies and classifies a population of human cross-tissue ILC1s.
第一组固有淋巴细胞(ILC)包括一组异质的细胞毒性自然杀伤(NK)细胞和 ILC1。我们鉴定出一群具有独特转录、表型和功能特征的“肝型”ILC1,与传统和肝驻留 NK 细胞以及其他先前描述的人类 ILC1 亚群不同。LT-ILC1 是 CD49aCD94CD200R1,表达转录因子 T-BET,不表达激活受体 NKp80 或转录因子 EOMES。与 NK 细胞类似,肝型 ILC1 产生 IFN-γ、TNF-α 和 GM-CSF;然而,肝型 ILC1 还产生 IL-2,并且缺乏穿孔素和颗粒酶 B。肝型 ILC1 在肝硬化肝组织中扩增,并且可以在 TGF-β1 和肝窦内皮细胞存在的情况下从血液衍生的 ILC 前体在体外产生。在扁桃体和肠道组织中也可以发现具有相似特征和功能的细胞。总之,我们的研究鉴定并分类了一群人类跨组织 ILC1。