Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Nat Immunol. 2024 Aug;25(8):1460-1473. doi: 10.1038/s41590-024-01885-y. Epub 2024 Jul 2.
Group 1 innate lymphoid cells (ILC1s) are cytotoxic and interferon gamma-producing lymphocytes lacking antigen-specific receptors, which include ILC1s and natural killer (NK) cells. In mice, ILC1s differ from NK cells, as they develop independently of the NK-specifying transcription factor EOMES, while requiring the repressor ZFP683 (ZNF683 in humans) for tissue residency. Here we identify highly variable ILC1 subtypes across tissues through investigation of human ILC1 diversity by single-cell RNA sequencing and flow cytometry. The intestinal epithelium contained abundant mature EOMES ILC1s expressing PRDM1 rather than ZNF683, alongside a few immature TCF7PRDM1 ILC1s. Other tissues harbored NK cells expressing ZNF683 and EOMES transcripts; however, EOMES protein content was variable. These ZNF683 NK cells are tissue-imprinted NK cells phenotypically resembling ILC1s. The tissue ILC1-NK spectrum also encompassed conventional NK cells and NK cells distinguished by PTGDS expression. These findings establish a foundation for evaluating phenotypic and functional changes within the NK-ILC1 spectrum in diseases.
第一组固有淋巴细胞 (ILC1) 是细胞毒性和产生干扰素 γ 的淋巴细胞,缺乏抗原特异性受体,包括 ILC1 和自然杀伤 (NK) 细胞。在小鼠中,ILC1 与 NK 细胞不同,因为它们独立于 NK 特异性转录因子 EOMES 发育,而需要抑制因子 ZFP683(人类中的 ZNF683)来维持组织驻留。在这里,我们通过单细胞 RNA 测序和流式细胞术研究人类 ILC1 的多样性,鉴定了不同组织中高度可变的 ILC1 亚型。肠道上皮含有丰富的表达 PRDM1 而不是 ZNF683 的成熟 EOMES ILC1,以及少数不成熟的 TCF7PRDM1 ILC1。其他组织中存在表达 ZNF683 和 EOMES 转录本的 NK 细胞;然而,EOMES 蛋白含量是可变的。这些 ZNF683 NK 细胞是组织印迹的 NK 细胞,表型类似于 ILC1。组织 ILC1-NK 谱还包括常规 NK 细胞和通过 PTGDS 表达区分的 NK 细胞。这些发现为评估疾病中 NK-ILC1 谱内的表型和功能变化奠定了基础。