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Mammary intraepithelial lymphocytes and intestinal inputs shape T cell dynamics in lactogenesis 乳腺上皮内淋巴细胞和肠道输入形成乳发生中的T细胞动力学
IF 27.6 1区 医学
Nature Immunology Pub Date : 2025-07-29 DOI: 10.1038/s41590-025-02218-3
Abigail Jaquish, Eleni Phung, Xutong Gong, Pilar Baldominos, Silvia Galván-Peña, Ian Magill, Isabelle Bursulaya, Eleonora Marina, ImmgenT consortium, Kerri Bertrand, Christina Chambers, Andrés R. Muñoz-Rojas, Judith Agudo, Diane Mathis, Christophe Benoist, Deepshika Ramanan
{"title":"Mammary intraepithelial lymphocytes and intestinal inputs shape T cell dynamics in lactogenesis","authors":"Abigail Jaquish, Eleni Phung, Xutong Gong, Pilar Baldominos, Silvia Galván-Peña, Ian Magill, Isabelle Bursulaya, Eleonora Marina, ImmgenT consortium, Kerri Bertrand, Christina Chambers, Andrés R. Muñoz-Rojas, Judith Agudo, Diane Mathis, Christophe Benoist, Deepshika Ramanan","doi":"10.1038/s41590-025-02218-3","DOIUrl":"10.1038/s41590-025-02218-3","url":null,"abstract":"Pregnancy brings about profound changes in the mammary gland to prepare for lactation, yet immunocyte changes that accompany this rapid remodeling are incompletely understood. We comprehensively analyzed mammary T cells, revealing a marked increase in CD4+ and CD8+ T effector cells, including an expansion of T cell receptor (TCR)αβ+CD8αα+ cells, in pregnancy and lactation. T cells were localized in the mammary epithelium, resembling intraepithelial lymphocytes (IELs) typically found in mucosal tissues. Similarity to mucosal tissues was substantiated by demonstrating partial dependence on microbial cues, T cell migration from the intestine to the mammary gland in late pregnancy and shared TCR clonotypes between intestinal and mammary tissues, including intriguing public TCR families. Putative counterparts of mammary IELs were found in human breast and milk. Mammary IELs are thus poised to manage the transition from a nonmucosal tissue to a mucosal barrier during lactogenesis. Here Ramanan and colleagues provide an analysis of mammary T cells during late pregnancy and lactation. This revealed an increase in intraepithelial lymphocytes in the lactating mammary gland, which was driven by thymic and intestinal inputs and was sensitive to changes in the microbiota","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 8","pages":"1411-1422"},"PeriodicalIF":27.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736772","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}
引用次数: 0
PD-1 is requisite for skin TRM cell formation and specification by TGFβ PD-1是皮肤TRM细胞形成和TGFβ规范所必需的
IF 27.6 1区 医学
Nature Immunology Pub Date : 2025-07-29 DOI: 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}
引用次数: 0
Targeting CAFs 针对战乱国家
IF 27.6 1区 医学
Nature Immunology Pub Date : 2025-07-29 DOI: 10.1038/s41590-025-02248-x
Nicholas J. Bernard
{"title":"Targeting CAFs","authors":"Nicholas J. Bernard","doi":"10.1038/s41590-025-02248-x","DOIUrl":"10.1038/s41590-025-02248-x","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":"144737076","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}
引用次数: 0
Intraepithelial T cells move from gut to breast to shape lactation 上皮内T细胞从肠道转移到乳房形成泌乳
IF 27.6 1区 医学
Nature Immunology Pub Date : 2025-07-29 DOI: 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}
引用次数: 0
The immunology of asthma 哮喘的免疫学
IF 27.6 1区 医学
Nature Immunology Pub Date : 2025-07-29 DOI: 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}
引用次数: 0
Anti-tumor immunity is boosted by loss of TGFβ-driven tissue residency 抗肿瘤免疫通过tgf β驱动的组织驻留的丧失而增强
IF 27.6 1区 医学
Nature Immunology Pub Date : 2025-07-29 DOI: 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}
引用次数: 0
Lymph-node-derived stem-like but not tumor-tissue-resident CD8+ T cells fuel anticancer immunity 淋巴结衍生的干细胞样而非肿瘤组织驻留的CD8+ T细胞可促进抗癌免疫
IF 27.6 1区 医学
Nature Immunology Pub Date : 2025-07-29 DOI: 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}
引用次数: 0
Carboxylation switch 羧化作用开关
IF 27.6 1区 医学
Nature Immunology Pub Date : 2025-07-29 DOI: 10.1038/s41590-025-02249-w
Ioana Staicu
{"title":"Carboxylation switch","authors":"Ioana Staicu","doi":"10.1038/s41590-025-02249-w","DOIUrl":"10.1038/s41590-025-02249-w","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":"144736799","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}
引用次数: 0
TLRs are blind to pseudouridine RNA tlr对假尿嘧啶RNA不可见
IF 27.6 1区 医学
Nature Immunology Pub Date : 2025-07-29 DOI: 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}
引用次数: 0
The impact of genetic immune disorders on infections including COVID-19, inflammatory bowel disease and cancer 遗传免疫疾病对感染的影响，包括COVID-19、炎症性肠病和癌症
IF 27.6 1区 医学
Nature Immunology Pub Date : 2025-07-28 DOI: 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}
引用次数: 0
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