Nature ImmunologyPub Date : 2025-07-29DOI: 10.1038/s41590-025-02228-1
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 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":"10.1038/s41590-025-02228-1","url":null,"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. Anandasabapathy and colleagues show that the inhibitory receptor PD-1 impacts the specification of tissue-resident memory T cells in the skin.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 8","pages":"1339-1351"},"PeriodicalIF":27.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41590-025-02228-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature ImmunologyPub Date : 2025-07-29DOI: 10.1038/s41590-025-02221-8
Amanpreet Singh Chawla, Mahima Swamy
{"title":"Intraepithelial T cells move from gut to breast to shape lactation","authors":"Amanpreet Singh Chawla, Mahima Swamy","doi":"10.1038/s41590-025-02221-8","DOIUrl":"10.1038/s41590-025-02221-8","url":null,"abstract":"During late gestation, unconventional intraepithelial αβ T cells migrate from the gut to the mammary gland to remodel the tissue for lactation and enhance its mucosal barrier state.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 8","pages":"1219-1220"},"PeriodicalIF":27.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature ImmunologyPub Date : 2025-07-29DOI: 10.1038/s41590-025-02212-9
Bart N. Lambrecht, Engi Ahmed, Hamida Hammad
{"title":"The immunology of asthma","authors":"Bart N. Lambrecht, Engi Ahmed, Hamida Hammad","doi":"10.1038/s41590-025-02212-9","DOIUrl":"10.1038/s41590-025-02212-9","url":null,"abstract":"Asthma is a chronic inflammatory disease of the airways characterized by variable airway obstruction. In some patients with severe disease there are frequent disease flares, and some individuals develop irreversible airway obstruction. The immune system has a predominant effect on many aspects of the disease. A large proportion of people with asthma have signs of type 2 immunity, rich in eosinophils, mast cells and basophils, and controlled by either type 2 helper T cells or type 2 innate lymphoid cells. Other patients have a more neutrophil-predominant disease, and some have little underlying immune dysfunction. Here we review the immunology of asthma by integrating data from mouse model studies with clinical intervention studies. In this Review, the authors update us on the immunology and clinical options for treating asthma.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 8","pages":"1233-1245"},"PeriodicalIF":27.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature ImmunologyPub Date : 2025-07-29DOI: 10.1038/s41590-025-02224-5
Dongmei Zhao, Hai-Hui Xue
{"title":"Anti-tumor immunity is boosted by loss of TGFβ-driven tissue residency","authors":"Dongmei Zhao, Hai-Hui Xue","doi":"10.1038/s41590-025-02224-5","DOIUrl":"10.1038/s41590-025-02224-5","url":null,"abstract":"Tumor-infiltrating CD8+ T cells acquire HOBIT expression and features of tissue-resident memory cells. This TGFβ-driven process is dispensable for tumor control by immune checkpoint blockade, but disrupting TGFβ signaling in HOBIT-expressing tumor-infiltrating lymphocytes enhances anti-tumor immunity.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 8","pages":"1223-1224"},"PeriodicalIF":27.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature ImmunologyPub Date : 2025-07-29DOI: 10.1038/s41590-025-02219-2
Sharanya K. M. Wijesinghe, Lisa Rausch, Sarah S. Gabriel, Giovanni Galletti, Marco De Luca, Lei Qin, Lifen Wen, Carlson Tsui, Kevin Man, Leonie Heyden, Teisha Mason, Lewis D. Newland, Andrew Kueh, Yang Liao, David Chisanga, Julian Swatler, Emanuele Voulaz, Giuseppe Marulli, Valentina Errico, Agnese Losurdo, Gustavo R. Rossi, Fernando Souza-Fonseca-Guimaraes, Nicholas D. Huntington, Thomas Gebhardt, Daniel T. Utzschneider, Marco J. Herold, Wei Shi, Jan Schroeder, Enrico Lugli, Axel Kallies
{"title":"Lymph-node-derived stem-like but not tumor-tissue-resident CD8+ T cells fuel anticancer immunity","authors":"Sharanya K. M. Wijesinghe, Lisa Rausch, Sarah S. Gabriel, Giovanni Galletti, Marco De Luca, Lei Qin, Lifen Wen, Carlson Tsui, Kevin Man, Leonie Heyden, Teisha Mason, Lewis D. Newland, Andrew Kueh, Yang Liao, David Chisanga, Julian Swatler, Emanuele Voulaz, Giuseppe Marulli, Valentina Errico, Agnese Losurdo, Gustavo R. Rossi, Fernando Souza-Fonseca-Guimaraes, Nicholas D. Huntington, Thomas Gebhardt, Daniel T. Utzschneider, Marco J. Herold, Wei Shi, Jan Schroeder, Enrico Lugli, Axel Kallies","doi":"10.1038/s41590-025-02219-2","DOIUrl":"10.1038/s41590-025-02219-2","url":null,"abstract":"CD8+ T cell-mediated tumor control and efficacy of immune checkpoint blockade (ICB) are associated with both precursors of exhausted T (TPEX) cells and tissue-resident memory T cells. Their relationships and relative contribution to tumor control, however, are insufficiently understood. Using single-cell RNA sequencing and genetic mouse models, we systematically dissected the heterogeneity and function of cytotoxic T cells in tumors and tumor-draining lymph nodes (tdLNs). We found that intratumoral TCF1+ TPEX cells and their progeny acquired a tissue-residency program that limits their contribution to tumor control and ICB response. By contrast, MYB-dependent stem-like TPEX cells residing in tdLNs sustained CD8+ T cell infiltration into tumors and mediated ICB response. The cytokine TGFβ was the central factor that enforced residency of intratumoral CD8+ T cells and limited the abundance of stem-like TPEX cells in tdLNs, thereby restraining tumor control. A similar network of TGFβ-constrained intratumoral and extratumoral CD8+ T cells with precursor and residency characteristics was found in human cancer. Here the authors dissect the developmental and functional relationship between tumor-responsive cytotoxic T cells in the tumor versus the tumor-draining lymph nodes (tdLNs), finding that stem-like TPEX cells dependent on MYB in the tdLNs are required for CD8⁺ T cell tumor infiltration and ICB responses.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 8","pages":"1367-1383"},"PeriodicalIF":27.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature ImmunologyPub Date : 2025-07-29DOI: 10.1038/s41590-025-02251-2
Paula Jauregui
{"title":"TLRs are blind to pseudouridine RNA","authors":"Paula Jauregui","doi":"10.1038/s41590-025-02251-2","DOIUrl":"10.1038/s41590-025-02251-2","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 8","pages":"1213-1213"},"PeriodicalIF":27.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature ImmunologyPub Date : 2025-07-28DOI: 10.1038/s41590-025-02225-4
Chen Xiang, Ann Y. Park, Sarah E. Weber, Michael J. Lenardo, Ahmet Ozen, Jing Cui
{"title":"The impact of genetic immune disorders on infections including COVID-19, inflammatory bowel disease and cancer","authors":"Chen Xiang, Ann Y. Park, Sarah E. Weber, Michael J. Lenardo, Ahmet Ozen, Jing Cui","doi":"10.1038/s41590-025-02225-4","DOIUrl":"10.1038/s41590-025-02225-4","url":null,"abstract":"Inborn errors of immunity (IEIs) are rare genetic anomalies that cause defective immune function. Over 500 IEIs have been identified to date, affecting millions of patients globally. These IEIs reveal the complex interplay between genetics, the environment and microorganisms that determine immune disease phenotypes. Progress in understanding the molecular and cellular mechanisms of IEIs provides a genetic framework for a functional understanding of the human immune system, disease pathogenesis and successful therapeutic interventions. This Review describes how IEIs impact infectious diseases, particularly coronavirus disease 2019, inflammatory bowel disease and cancer. Cui et al. discuss new molecular and cellular insights underlying the pathogenesis of rare human diseases that arise from genetic inborn errors of immunity.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 9","pages":"1440-1452"},"PeriodicalIF":27.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nature ImmunologyPub Date : 2025-07-25DOI: 10.1038/s41590-025-02244-1
{"title":"Aberrant protein translation promotes T cell exhaustion","authors":"","doi":"10.1038/s41590-025-02244-1","DOIUrl":"10.1038/s41590-025-02244-1","url":null,"abstract":"Adoptive T cell therapies show limited efficacy against solid tumors owing to T cell exhaustion within the tumor microenvironment. A study now reveals that dysregulated translation, rather than transcriptional changes alone, drives T cell dysfunction by creating mitochondrial imbalance through selective protein synthesis.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 9","pages":"1438-1439"},"PeriodicalIF":27.6,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}