美国威尔康奈尔医学院Niroshana Anandasabapathy小组的研究显示，PD-1是皮肤T_RM细胞形成和TGFβ规范所必需的。相关论文于2025年7月29日发表在《自然—免疫学》杂志上。

该研究团队发现，通过免疫检查点程序性死亡受体1 （PD-1）的信号强烈影响皮肤中CD8⁺ T_RM细胞的早期规范。在没有持续感染的情况下，PD-1在小鼠和人类皮肤T_RM细胞中广泛表达，并且在老年小鼠皮肤TRM细胞中保留。PD-1支持早期T_RM细胞定植、皮肤特异性编程和其他分化程序的沉默，并促进TGFβ的反应性和皮肤植入。因此，PD-1信号在免疫启动过程中介导皮肤TRM细胞的分化。这些发现可能为PD-1受体激动剂和拮抗剂调节外周记忆提供了信息。

据悉，组织驻留记忆T（T_RM）细胞提供感染、癌症和疫苗训练的免疫跨越屏障部位。T_RM细胞参与自身免疫、肿瘤微环境中对免疫检查点阻断的成功应答以及外周组织中免疫检查点阻断后发生的毒性反应。

附：英文原文

Title: PD-1 is requisite for skin TRM cell formation and specification by TGFβ

Author: Devi, K. Sanjana P., Wang, Eric, Jaiswal, Abhinav, Konieczny, Piotr, Kim, Tae-Gyun, Nirschl, Christopher J., Verma, Akanksha, Liu, Yong, Milczanowski, Julia, Christo, Susan N., Gandolfo, Luke C., Haitz, Karyn, Vardam, Trupti D., Wu, Pinru, King, Sandra L., Tse, Sze-Wah, Pradhan, Komal, Jiang, Xiaodong, Tian, Tian, Fuhlbrigge, Robert C., Schmults, Chrysalyne D., Clark, Rachael A., Kupper, Thomas S., Freeman, Gordon J., Mackay, Laura K., Naik, Shruti, Newell, Evan W., Elemento, Olivier, Suarez-Farinas, Mayte, Anandasabapathy, Niroshana

Issue&Volume: 2025-07-29

Abstract: Tissue-resident memory T (TRM) cells provide infectious, cancer and vaccine-trained immunity across barrier sites. TRM cells are implicated in autoimmunity, successful response to immune checkpoint blockade in the tumor microenvironment and toxicities that occur after immune checkpoint blockade in peripheral tissues. Here, we identified that signaling through the immune checkpoint programmed death receptor 1 (PD-1) strongly impacts the early specification of CD8+ TRM cells in the skin. PD-1 is expressed broadly across mouse and human skin TRM cells, in the absence of persistent infection, and is retained on skin TRM cells in aged mice. PD-1 supports early TRM cell colonization, skin-specific programming and silencing of other differentiation programs and promotes TGFβ responsivity and skin engraftment. Thus, PD-1 signaling mediates skin TRM cell specification during immune initiation. These findings may inform therapeutic PD-1 agonist and antagonist use to modulate successful peripheral memory.

DOI: 10.1038/s41590-025-02228-1

Source: https://www.nature.com/articles/s41590-025-02228-1