美国华盛顿大学医学院Marco Colonna及其小组的研究揭示了人组织中第1组先天淋巴样细胞（ILC1s）的多样性。相关论文于2024年7月2日发表在《自然-免疫学》杂志上。

研究人员通过单细胞RNA测序和流式细胞技术研究了人ILC1的多样性，确定了不同组织中高度可变的ILC1亚型。肠上皮细胞中含有大量表达PRDM1而非ZNF683的成熟EOMES-ILC1，以及少量未成熟TCF7⁺PRDM1-ILC1。其他组织中也有表达ZNF683和EOMES转录本的自然杀伤（NK）细胞，但EOMES蛋白含量不一。这些ZNF683⁺ NK细胞的表型类似于ILC1的组织印迹NK细胞。组织ILC1-NK谱系还包括传统的NK细胞和通过表达PTGDS区分的NK细胞。这些发现为评估疾病中NK-ILC1谱系的表型和功能变化奠定了基础。

据悉，ILC1是细胞毒性和产生γ干扰素的淋巴细胞，缺乏抗原特异性受体，包括ILC1s和NK细胞。在小鼠体内，ILC1s与NK细胞不同，它们的发育不依赖于NK特异性转录因子EOMES，而需要抑制因子ZFP683（在人类中为ZNF683）才能在组织中驻留。

附：英文原文

Title: Diversity of group 1 innate lymphoid cells in human tissues

Author: Jaeger, Natalia, Antonova, Alina Ulezko, Kreisel, Daniel, Roan, Florence, Lantelme, Erica, Ziegler, Steven F., Cella, Marina, Colonna, Marco

Issue&Volume: 2024-07-02

Abstract: 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 TCF7+PRDM1 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.

DOI: 10.1038/s41590-024-01885-y

Source: https://www.nature.com/articles/s41590-024-01885-y