德国弗莱堡大学医学院Sagar研究团队利用多模态分析，揭示了小鼠γδ T细胞跨器官的位点特异性适应和组织驻留特征。相关论文于2024年1月4日发表于国际顶尖学术期刊《自然—免疫学》杂志上。

通过跨器官多模态单细胞分析，他们发现各种小鼠组织都有独特的位点适应γδ亚群。表皮和肠上皮内γδ T细胞在转录上是同质的，并表现出功能多样性的表观遗传特征。通过异种共生实验，他们发现细胞状态与细胞毒性、先天样的快速干扰素-γ产生和组织修复功能相关，显示出组织驻留特征。值得注意的是，他们的观察增加了产生白细胞介素17的γδ T细胞和组织驻留之间的联系的细微差别。

此外，与组织驻留γδ T细胞相关的转录程序类似于CD8+组织驻留记忆T细胞。总之，本研究提供了组织适应γδ T细胞的多模态景观，揭示了异质性，谱系关系及其组织驻留计划。

据了解，γδ T细胞在组织内稳态和疾病中发挥异质功能。然而，尚不清楚这些作用是否对应于不同的γδ亚群，还是对应于发挥上下文依赖功能的同质细胞群。

附：英文原文

Title: Multimodal profiling reveals site-specific adaptation and tissue residency hallmarks of γδ T cells across organs in mice

Author: du Halgouet, Anastasia, Bruder, Kerstin, Peltokangas, Nina, Darbois, Aurlie, Obwegs, David, Salou, Marion, Thimme, Robert, Hofmann, Maike, Lantz, Olivier, Sagar

Issue&Volume: 2024-01-04

Abstract: γδ T cells perform heterogeneous functions in homeostasis and disease across tissues. However, it is unclear whether these roles correspond to distinct γδ subsets or to a homogeneous population of cells exerting context-dependent functions. Here, by cross-organ multimodal single-cell profiling, we reveal that various mouse tissues harbor unique site-adapted γδ subsets. Epidermal and intestinal intraepithelial γδ T cells are transcriptionally homogeneous and exhibit epigenetic hallmarks of functional diversity. Through parabiosis experiments, we uncovered cellular states associated with cytotoxicity, innate-like rapid interferon-γ production and tissue repair functions displaying tissue residency hallmarks. Notably, our observations add nuance to the link between interleukin-17-producing γδ T cells and tissue residency. Moreover, transcriptional programs associated with tissue-resident γδ T cells are analogous to those of CD8+ tissue-resident memory T cells. Altogether, this study provides a multimodal landscape of tissue-adapted γδ T cells, revealing heterogeneity, lineage relationships and their tissue residency program.

DOI: 10.1038/s41590-023-01710-y

Source: https://www.nature.com/articles/s41590-023-01710-y