Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Immunity. 2021 Jun 8;54(6):1320-1337.e4. doi: 10.1016/j.immuni.2021.03.024. Epub 2021 May 3.
Natural killer (NK) cells and type 1 innate lymphoid cells (ILC1s) are heterogenous innate lymphocytes broadly defined in mice as LinNK1.1NKp46 cells that express the transcription factor T-BET and produce interferon-γ. The ILC1 definition primarily stems from studies on liver and small intestinal populations. However, NK1.1NKp46 cells in the salivary glands, uterus, adipose, and other tissues exhibit nonuniform programs that differ from those of liver or intestinal ILC1s or NK cells. Here, we performed single-cell RNA sequencing on murine NK1.1NKp46 cells from blood, spleen, various tissues, and solid tumors. We identified gene expression programs of tissue-specific ILC1s, tissue-specific NK cells, and non-tissue-specific populations in blood, spleen, and other tissues largely corresponding to circulating cells. Moreover, we found that circulating NK cell programs were reshaped in tumor-bearing mice. Core programs of circulating and tumor NK cells paralleled conserved human NK cells signatures, advancing our understanding of the human NK-ILC1 spectrum.
自然杀伤 (NK) 细胞和 1 型先天淋巴细胞 (ILC1) 是广泛定义在小鼠中的异质性先天淋巴细胞，被定义为 LinNK1.1NKp46 细胞，这些细胞表达转录因子 T-BET 并产生干扰素-γ。ILC1 的定义主要源于对肝脏和小肠群体的研究。然而，唾液腺、子宫、脂肪组织和其他组织中的 NK1.1NKp46 细胞表现出与肝脏或肠道 ILC1 或 NK 细胞不同的非均匀程序。在这里，我们对来自血液、脾脏、各种组织和实体瘤的小鼠 NK1.1NKp46 细胞进行了单细胞 RNA 测序。我们确定了血液、脾脏和其他组织中组织特异性 ILC1、组织特异性 NK 细胞和非组织特异性群体的基因表达程序，这些程序与循环细胞基本对应。此外，我们发现荷瘤小鼠的循环 NK 细胞程序发生了重塑。循环和肿瘤 NK 细胞的核心程序与保守的人类 NK 细胞特征平行，这推进了我们对人类 NK-ILC1 谱的理解。
