美国加州大学Ananda W. Goldrath近期取得重要工作进展，他们研究发现组织驻留记忆CD8⁺ T细胞对不同组织环境具有独特的转录、表观遗传和功能适应性。相关研究成果2022年6月27日在线发表于《自然—免疫学》杂志上。

在本研究中，来自不同器官的小鼠CD8⁺ T_RM细胞对病毒感染作出反应的基因表达和基因组可及性的多样性，揭示了共享的和组织特异性的转录和表观遗传特征。肠道和唾液腺中的T_RM细胞表达转化生长因子(TGF)-β诱导的基因，并通过持续的TGF-β信号传导来维持，而脂肪、肾脏和肝脏中的T_RM细胞则不然。构建转录调控网络将转录抑制因子Hic1鉴定为小肠T_RM细胞分化的关键调节因子，并表明Hic1过表达增强了T_RM细胞分化和免受感染。

研究人员提供一个框架来了解CD8⁺T_RM细胞如何适应不同的组织环境，并确定介导这些适应的组织特异性转录调节因子，为增强最易受感染部位的保护性记忆反应提供策略。

据介绍，组织驻留记忆T细胞 (T_RM细胞) 提供保护性免疫，但特定组织环境对T_RM细胞分化和体内平衡的贡献尚不清楚。

附：英文原文

Title: Tissue-resident memory CD8+ T cells possess unique transcriptional, epigenetic and functional adaptations to different tissue environments

Author: Crowl, John T., Heeg, Maximilian, Ferry, Amir, Milner, J. Justin, Omilusik, Kyla D., Toma, Clara, He, Zhaoren, Chang, John T., Goldrath, Ananda W.

Issue&Volume: 2022-06-27

Abstract: Tissue-resident memory T cells (TRM cells) provide protective immunity, but the contributions of specific tissue environments to TRM cell differentiation and homeostasis are not well understood. In the present study, the diversity of gene expression and genome accessibility by mouse CD8+ TRM cells from distinct organs that responded to viral infection revealed both shared and tissue-specific transcriptional and epigenetic signatures. TRM cells in the intestine and salivary glands expressed transforming growth factor (TGF)-β-induced genes and were maintained by ongoing TGF-β signaling, whereas those in the fat, kidney and liver were not. Constructing transcriptional–regulatory networks identified the transcriptional repressor Hic1 as a critical regulator of TRM cell differentiation in the small intestine and showed that Hic1 overexpression enhanced TRM cell differentiation and protection from infection. Provision of a framework for understanding how CD8+ TRM cells adapt to distinct tissue environments, and identification of tissue-specific transcriptional regulators mediating these adaptations, inform strategies to boost protective memory responses at sites most vulnerable to infection.

DOI: 10.1038/s41590-022-01229-8

Source: https://www.nature.com/articles/s41590-022-01229-8