Lan Zhiyi, Chen Zeyu, Yang Nan, Liu Tong, Li Siqi, Shi Yuling, Gu Jun
Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China.
Institute of Psoriasis, Tongji University School of Medicine, Shanghai, China.
Front Immunol. 2025 Aug 15;16:1605972. doi: 10.3389/fimmu.2025.1605972. eCollection 2025.
Tissue-resident memory T cells (TRM) represent a heterogeneous population of T cells that exhibit both effector and memory functionalities. They express specific gene signatures that enable them to occupy tissues without recirculating, thus providing a first response against reencountered pathogens or antigens. TRM have been implicated in the pathogenesis of various diseases, including autoimmune disorders, infections, and cancers. This has prompted interest in targeting TRM as a potential therapeutic strategy. Epigenetic modifications, which frequently occur in immune cells across various disease states, play a significant role not only in tissue homeostasis but also in disease progression. Emerging evidence suggests that the epigenetic landscape of TRM is altered in pathogenic conditions, impacting their differentiation, maintenance, and function. Nevertheless, the precise mechanisms remain poorly understood. This review seeks to provide a comprehensive overview of the epigenetic regulation of TRM, focusing on key areas such as chromatin accessibility, DNA methylation, histone modifications, and non-coding RNAs. Importantly, a deeper understanding of these epigenetic mechanisms will pave the way for novel therapeutic strategies, such as modulating TRM activity in autoimmune diseases, enhancing tissue-specific immunity through vaccines, or improving immunotherapeutic efficacy in cancer.
组织驻留记忆T细胞（TRM）是一类异质性T细胞群体，兼具效应器和记忆功能。它们表达特定的基因特征，使其能够定位于组织中而不进行再循环，从而对再次遇到的病原体或抗原提供初次应答。TRM已被证明与包括自身免疫性疾病、感染和癌症在内的多种疾病的发病机制有关。这引发了将TRM作为一种潜在治疗策略的研究兴趣。表观遗传修饰在各种疾病状态下的免疫细胞中频繁发生，不仅在组织稳态中起重要作用，还在疾病进展中发挥作用。新出现的证据表明，在致病条件下TRM的表观遗传格局会发生改变，影响其分化、维持和功能。然而，其确切机制仍知之甚少。本综述旨在全面概述TRM的表观遗传调控，重点关注染色质可及性、DNA甲基化、组蛋白修饰和非编码RNA等关键领域。重要的是，对这些表观遗传机制的更深入理解将为新的治疗策略铺平道路，例如在自身免疫性疾病中调节TRM活性、通过疫苗增强组织特异性免疫或提高癌症免疫治疗效果。
