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
Department of Dermatology, Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
Department of Immunology and Immunotherapy, Icahn School of Medicine at Mt. Sinai, New York, NY, USA.
Nat Immunol. 2025 Aug;26(8):1339-1351. doi: 10.1038/s41590-025-02228-1. Epub 2025 Jul 29.
Tissue-resident memory T (T) cells provide infectious, cancer and vaccine-trained immunity across barrier sites. T 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 T cells in the skin. PD-1 is expressed broadly across mouse and human skin T cells, in the absence of persistent infection, and is retained on skin T cells in aged mice. PD-1 supports early T cell colonization, skin-specific programming and silencing of other differentiation programs and promotes TGFβ responsivity and skin engraftment. Thus, PD-1 signaling mediates skin T cell specification during immune initiation. These findings may inform therapeutic PD-1 agonist and antagonist use to modulate successful peripheral memory.
组织驻留记忆T（TRM）细胞在屏障部位提供抗感染、抗癌和疫苗诱导的免疫。TRM细胞与自身免疫、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免疫检查点阻断后出现的毒性有关。在这里，我们发现通过免疫检查点程序性死亡受体1（PD-1）发出的信号强烈影响皮肤中CD8 T细胞的早期分化。在没有持续感染的情况下，PD-1在小鼠和人类皮肤T细胞中广泛表达，并且在老年小鼠的皮肤T细胞中持续存在。PD-1支持早期T细胞定植、皮肤特异性编程以及其他分化程序的沉默，并促进TGFβ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T细胞分化。这些发现可能为治疗性使用PD-1激动剂和拮抗剂以调节成功的外周记忆提供依据。
