Wenji Piao, Zachariah L. Lee, Gregory Zapas, Long Wu, Christopher M. Jewell, Reza Abdi, Jonathan S. Bromberg
{"title":"Regulatory T cell and endothelial cell crosstalk","authors":"Wenji Piao, Zachariah L. Lee, Gregory Zapas, Long Wu, Christopher M. Jewell, Reza Abdi, Jonathan S. Bromberg","doi":"10.1038/s41577-025-01149-2","DOIUrl":"https://doi.org/10.1038/s41577-025-01149-2","url":null,"abstract":"<p>Regulatory T (T<sub>reg</sub>) cells have a central role in the maintenance of immune surveillance and tolerance. They can migrate from lymphoid organs to blood and then into tissues and egress from tissues into draining lymph nodes. Specialized endothelial cells of blood and lymphatic vessels are the key gatekeepers for these processes. T<sub>reg</sub> cells that transmigrate across single-cell layers of endothelial cells engage in bidirectional crosstalk with these cells and regulate vascular permeability by promoting structural modifications of blood and lymphatic endothelial cells. In turn, blood and lymphatic endothelial cells can modulate T<sub>reg</sub> cell recirculation and residency. Here, we discuss recent insights into the cellular and molecular mechanisms of the crosstalk between T<sub>reg</sub> cells and endothelial cells and explore potential therapeutic strategies to target these interactions in autoimmunity, transplantation and cancer.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"56 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758181","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}
{"title":"Macrophages promote nerve growth in both tumours and spinal cord","authors":"Austeja Baleviciute, Sebastien Talbot","doi":"10.1038/s41577-025-01164-3","DOIUrl":"https://doi.org/10.1038/s41577-025-01164-3","url":null,"abstract":"A preprint by Dolci et al. reports that tumour-associated macrophages secrete SPP1 to drive neurite outgrowth, promoting tumour innervation and spinal cord repair.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"72 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723161","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}
{"title":"Resident tissue macrophages maintain intraocular pressure by regulating extracellular matrix homeostasis","authors":"Alex Lac, Slava Epelman","doi":"10.1038/s41577-025-01163-4","DOIUrl":"https://doi.org/10.1038/s41577-025-01163-4","url":null,"abstract":"A preprint by Liu et al. shows that resident tissue macrophages in the conventional outflow tract regulate intraocular pressure in the steady state.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"41 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723121","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}
{"title":"Early antiviral type I interferon impairs lung metastasis","authors":"Lisha Jeena, Ester Gea-Mallorquí","doi":"10.1038/s41577-025-01165-2","DOIUrl":"https://doi.org/10.1038/s41577-025-01165-2","url":null,"abstract":"A preprint by Farias et al. shows that the type I interferon response to respiratory syncytial virus infection reduces lung metastasis of breast cancer in a mouse model.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"118 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712738","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}
{"title":"New insights into antibody structure with implications for specificity, variable region restriction and isotype choice","authors":"Scott A. McConnell, Arturo Casadevall","doi":"10.1038/s41577-025-01150-9","DOIUrl":"https://doi.org/10.1038/s41577-025-01150-9","url":null,"abstract":"<p>The mystery surrounding the mechanisms by which antibody diversity is generated was largely settled in the 1970s by the discoveries of variable gene rearrangements and somatic hypermutation. This led to the paradigm that immunoglobulins are composed of two independent domains — variable and constant — that confer specificity and effector functions, respectively. However, since these early discoveries, there have been a series of observations of communication between the variable and constant domains that affects the overall antibody structure, which suggests that immunoglobulins have a more complex, interconnected functionality than previously thought. Another unresolved issue has been the genesis of ‘restricted’ antibody responses, characterized by the use of only a few variable region gene segments, despite the enormous potential combinatorial diversity. In this Perspective, we place recent findings related to immunoglobulin structure and function in the context of these immunologically important, historically unsolved problems to propose a new model for how antibody specificity is achieved without autoreactivity.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"91 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660363","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}
Mohottige D. Neranjan Tharuka, Asimina S. Courelli, Yuan Chen
{"title":"Immune regulation by the SUMO family","authors":"Mohottige D. Neranjan Tharuka, Asimina S. Courelli, Yuan Chen","doi":"10.1038/s41577-025-01155-4","DOIUrl":"https://doi.org/10.1038/s41577-025-01155-4","url":null,"abstract":"<p>Post-translational protein modifications by the small ubiquitin-like modifier (SUMO) family have been shown to regulate immune cells in the context of infection, autoimmunity and, more recently, cancer. Recent clinical trials investigating sumoylation inhibition as a therapeutic approach for cancer have established that sumoylation has important immune modulatory effects. Sumoylation suppresses transcription factors in innate immune cells and in cytotoxic T cells through the direct modification of these factors, which leads to the recruitment of transcriptional repressor complexes containing histone deacetylases. By contrast, in regulatory T cells and T helper 17 cells, sumoylation of transcription factors can enhance transcriptional activity by recruiting transcriptional coactivators. Sumoylation is also involved in the repression of <i>IFNB1</i> and endogenous retroviruses and is therefore important for regulating interferon expression. A central theme from literature is that the sumoylation of a group of proteins, instead of a single target, collectively contributes to the regulation of various immune processes. In this Review, we consider how these studies provide scientific basis for future exploration of SUMO-mediated immune modulation for the treatment of cancers and autoimmune disorders.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"91 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653337","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}
{"title":"Aspirin helps T cells to stop cancer spread","authors":"Yvonne Bordon","doi":"10.1038/s41577-025-01160-7","DOIUrl":"10.1038/s41577-025-01160-7","url":null,"abstract":"Drugs like aspirin can enhance the anti-metastatic activity of T cells by blocking a platelet-mediated pathway of suppression.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 4","pages":"230-230"},"PeriodicalIF":67.7,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635108","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}
Tobias Junt, Thomas Calzascia, Elisabetta Traggiai, André Nogueira da Costa, Peter Gergely, Georg Schett, Thomas Dörner, Richard M. Siegel
{"title":"Defining immune reset: achieving sustained remission in autoimmune diseases","authors":"Tobias Junt, Thomas Calzascia, Elisabetta Traggiai, André Nogueira da Costa, Peter Gergely, Georg Schett, Thomas Dörner, Richard M. Siegel","doi":"10.1038/s41577-025-01141-w","DOIUrl":"https://doi.org/10.1038/s41577-025-01141-w","url":null,"abstract":"<p>Personalized cell therapies for autoimmune diseases — such as autologous haematopoietic stem cell transplantation and chimeric antigen receptor-expressing T cells — have the potential to achieve sustained remission in patients with certain autoimmune diseases. The effective elimination of pathogenic lymphocytes and their subsequent repopulation with naive cells has been termed ‘immune reset’. In this Perspective, we trace the origins of the immune reset concept and its clinical, cellular and molecular definitions, and we review current attempts to identify biomarkers for long-term clinical remission in autoimmune diseases. Emerging data from clinical trials support the concept that higher probabilities of long-term remission can be achieved with therapies that can more deeply and broadly deplete B cells than the anti-CD20 antibody rituximab. A better understanding of the cellular and molecular basis for immune reset and the biomarkers associated with this state should accelerate progress towards the goal of restoring a non-autoimmune state and sustaining remission, while reducing the need for chronic immunosuppression.</p>","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"194 1","pages":""},"PeriodicalIF":100.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546020","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}
{"title":"Neutrophils are dispensable for Shigella control: macrophages take centre stage","authors":"Didem Ağaç Çobanoğlu, James P. Allison","doi":"10.1038/s41577-025-01157-2","DOIUrl":"10.1038/s41577-025-01157-2","url":null,"abstract":"A preprint by Eislmayr et al. shows that macrophages rather than neutrophils are a key factor in controlling Shigella infection.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 4","pages":"233-233"},"PeriodicalIF":67.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546017","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}
{"title":"Mapping the developmental trajectory and recruitment of memory-phenotype Ly49+CD8+ T cells","authors":"Guillaume J. Trusz, Verena van der Heide","doi":"10.1038/s41577-025-01156-3","DOIUrl":"10.1038/s41577-025-01156-3","url":null,"abstract":"A preprint by Laubreton et al. suggests a role for agonist selection and cytokine-driven bystander activation in the differentiation and recruitment of memory-phenotype Ly49+CD8+ T cells.","PeriodicalId":19049,"journal":{"name":"Nature Reviews Immunology","volume":"25 4","pages":"233-233"},"PeriodicalIF":67.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546018","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}