K. Sanjana P. Devi, Eric Wang, Abhinav Jaiswal, Piotr Konieczny, Tae-Gyun Kim, Christopher J. Nirschl, Akanksha Verma, Yong Liu, Julia Milczanowski, Susan N. Christo, Luke C. Gandolfo, Karyn Haitz, Trupti D. Vardam, Pinru Wu, Sandra L. King, Sze-Wah Tse, Komal Pradhan, Xiaodong Jiang, Tian Tian, Robert C. Fuhlbrigge, Chrysalyne D. Schmults, Rachael A. Clark, Thomas S. Kupper, Gordon J. Freeman, Laura K. Mackay, Shruti Naik, Evan W. Newell, Olivier Elemento, Mayte Suarez-Farinas, Niroshana Anandasabapathy
{"title":"PD-1是皮肤TRM细胞形成和TGFβ规范所必需的","authors":"K. Sanjana P. Devi, Eric Wang, Abhinav Jaiswal, Piotr Konieczny, Tae-Gyun Kim, Christopher J. Nirschl, Akanksha Verma, Yong Liu, Julia Milczanowski, Susan N. Christo, Luke C. Gandolfo, Karyn Haitz, Trupti D. Vardam, Pinru Wu, Sandra L. King, Sze-Wah Tse, Komal Pradhan, Xiaodong Jiang, Tian Tian, Robert C. Fuhlbrigge, Chrysalyne D. Schmults, Rachael A. Clark, Thomas S. Kupper, Gordon J. Freeman, Laura K. Mackay, Shruti Naik, Evan W. Newell, Olivier Elemento, Mayte Suarez-Farinas, Niroshana Anandasabapathy","doi":"10.1038/s41590-025-02228-1","DOIUrl":null,"url":null,"abstract":"<p>Tissue-resident memory T (T<sub>RM</sub>) cells provide infectious, cancer and vaccine-trained immunity across barrier sites. T<sub>RM</sub> 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<sup>+</sup> T<sub>RM</sub> cells in the skin. PD-1 is expressed broadly across mouse and human skin T<sub>RM</sub> cells, in the absence of persistent infection, and is retained on skin T<sub>RM</sub> cells in aged mice. PD-1 supports early T<sub>RM</sub> 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<sub>RM</sub> cell specification during immune initiation. These findings may inform therapeutic PD-1 agonist and antagonist use to modulate successful peripheral memory.</p>","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"1 1","pages":""},"PeriodicalIF":27.6000,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"PD-1 is requisite for skin TRM cell formation and specification by TGFβ\",\"authors\":\"K. Sanjana P. Devi, Eric Wang, Abhinav Jaiswal, Piotr Konieczny, Tae-Gyun Kim, Christopher J. Nirschl, Akanksha Verma, Yong Liu, Julia Milczanowski, Susan N. Christo, Luke C. Gandolfo, Karyn Haitz, Trupti D. Vardam, Pinru Wu, Sandra L. King, Sze-Wah Tse, Komal Pradhan, Xiaodong Jiang, Tian Tian, Robert C. Fuhlbrigge, Chrysalyne D. Schmults, Rachael A. Clark, Thomas S. Kupper, Gordon J. Freeman, Laura K. Mackay, Shruti Naik, Evan W. Newell, Olivier Elemento, Mayte Suarez-Farinas, Niroshana Anandasabapathy\",\"doi\":\"10.1038/s41590-025-02228-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Tissue-resident memory T (T<sub>RM</sub>) cells provide infectious, cancer and vaccine-trained immunity across barrier sites. T<sub>RM</sub> 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<sup>+</sup> T<sub>RM</sub> cells in the skin. PD-1 is expressed broadly across mouse and human skin T<sub>RM</sub> cells, in the absence of persistent infection, and is retained on skin T<sub>RM</sub> cells in aged mice. PD-1 supports early T<sub>RM</sub> 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<sub>RM</sub> cell specification during immune initiation. These findings may inform therapeutic PD-1 agonist and antagonist use to modulate successful peripheral memory.</p>\",\"PeriodicalId\":19032,\"journal\":{\"name\":\"Nature Immunology\",\"volume\":\"1 1\",\"pages\":\"\"},\"PeriodicalIF\":27.6000,\"publicationDate\":\"2025-07-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41590-025-02228-1\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41590-025-02228-1","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
PD-1 is requisite for skin TRM cell formation and specification by TGFβ
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.
期刊介绍：
Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.
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