2025年9月22日出版的《自然—免疫学》杂志发表了美国科学家的一项最新研究成果。来自韦恩州立大学医学院的Marta Rodriguez-Garcia团队发现，人类女性生殖道先天淋巴样细胞的空间和功能多样性可能有助于对HIV的抗病毒反应。

在这里，课题组人员通过光谱流式细胞术和CITE-seq，芯片细胞术在生殖器解剖区域的空间位置，分析了人类FGT ILC的多样性，并确定了稳态功能和抗病毒反应。小组发现了生殖ILC亚群在内稳态下的空间和功能特化，与年龄相关和妊娠相关的变化是分区的。CD161的表达差异区分ILC亚群预载细胞因子在稳定状态。研究组在子宫内膜中发现了一个独特的NKp44⁺CCR6⁺ ILC3亚群，该亚群在稳态状态下主动脱粒，位于B细胞和T细胞。相比之下，ILC1s分布分散，富集于子宫颈外，位于上皮附近。体外HIV刺激后，生殖器ILCs表现出快速的亚群特异性抗病毒反应。这些发现揭示了FGT ILCs独特的组织和亚群特异性特征及其对病毒刺激的即时反应能力，为未来研究确定ILCs在FGT粘膜免疫保护中的潜在作用提供了基础。

据悉，先天淋巴样细胞（ILCs）是组织驻留淋巴细胞，专门分泌缺乏抗原特异性受体的细胞因子。ILCs对人类，特别是女性生殖道（FGT）的抗病毒粘膜免疫的贡献仍未被探索。

附：英文原文

Title: Spatial and functional diversity of innate lymphoid cells in the human female genital tract may contribute to antiviral responses to HIV

Author: Werner, Alexandra, Moreno de Lara, Laura, Holmes, Aleah, Parthasarathy, Siddharth, Moldovan, Genna E., Borchers, Anna, Carrillo-Salinas, Francisco J., Fortier, Jared M., Iyer, Vidya, Vogell, Alison, Jameson, Rebecca, Stephens, Jacquelyn, Rodriguez-Garcia, Marta

Issue&Volume: 2025-09-22

Abstract: Innate lymphoid cells (ILCs) are tissue-resident lymphocytes specialized in cytokine secretion that lack antigen-specific receptors. The contribution of ILCs to antiviral mucosal immunity in humans, particularly in the female genital tract (FGT), remains unexplored. Here we resolved human FGT ILC diversity by spectral flow cytometry and CITE-seq, spatial location within genital anatomical regions using ChipCytometry, and determined homeostatic function and antiviral responses. We uncovered spatial and functional specializations of genital ILC subsets under homeostasis, with compartmentalized age-related and pregnancy-related changes. CD161 expression differentially discriminated ILC subsets preloaded with cytokines at steady state. We identified a unique NKp44+CCR6+ ILC3 subset in the endometrium that actively degranulated at homeostasis and was located in lymphoid aggregates surrounded by Bcells and Tcells. By contrast, ILC1s were found scattered, enriched in the ectocervix and located close to the epithelium. Following in vitro HIV stimulation, genital ILCs displayed rapid subset-specific antiviral responses. These findings reveal distinct tissue and subset-specific features of FGT ILCs and their capacity to immediately respond to viral stimuli, providing a foundation for future studies to determine the potential role of ILCs in mucosal immune protection in the FGT.

DOI: 10.1038/s41590-025-02285-6

Source: https://www.nature.com/articles/s41590-025-02285-6