Nature Immunology最新文献

{"title":"Band-Aid for antibody production","authors":"Laurie A. Dempsey","doi":"10.1038/s41590-026-02497-4","DOIUrl":"10.1038/s41590-026-02497-4","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 4","pages":"639-639"},"PeriodicalIF":27.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147585345","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":"Blood vessel-resident macrophages safeguard blood and vessel integrity in zebrafish","authors":"Bart Weijts, Jeroen A. A. Demmers, Catherine Robin","doi":"10.1038/s41590-026-02481-y","DOIUrl":"10.1038/s41590-026-02481-y","url":null,"abstract":"Tissue-resident macrophages populate nearly all organs, where they adopt tissue-specific roles essential for immune defense, tissue development and homeostasis. Their dysfunction contributes to inflammation, cancer and other diseases. Whether a dedicated macrophage population operates within the extensive vascular network, one of the body’s largest and most widely distributed tissues, has remained unknown. Here, using high-resolution spatiotemporal live imaging in zebrafish embryos, we identify a distinct population of macrophages residing within blood vessels, termed blood vessel-resident macrophages (bMΦs), with conserved features in mice. bMΦs patrol the bloodstream, clear foreign particles and unfit cells, and act as first responders to endothelial damage. bMΦs emerge directly from axial vessels through an atypical endothelial-to-macrophage transition that is independent of Runx1 and Csf1r. Our findings reveal a previously unrecognized macrophage population dedicated to vascular immune surveillance, uncovering mechanisms that preserve blood and vessel integrity and offering potential therapeutic avenues for bloodborne and vascular diseases. Robin and colleagues describe a population of blood vessel-resident macrophages that function within the vasculature to maintain vascular and blood homeostasis in zebrafish and identify a conserved population of these cells in mice.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 5","pages":"975-984"},"PeriodicalIF":27.6,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41590-026-02481-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147584070","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}

{"title":"Sex differences in immune responses to viruses, bacteria and vaccines","authors":"Sabal Chaulagain, Jennifer A. Liu, Janet E. McCombs, Sabra L. Klein","doi":"10.1038/s41590-026-02470-1","DOIUrl":"10.1038/s41590-026-02470-1","url":null,"abstract":"Sex differences in immune function arise from sex chromosome complement, which drives differential expression and activity of X-linked genes in immune cells, and gonadal steroids that transcriptionally regulate innate and adaptive immune cells through their respective receptors. These fundamental differences shape divergent outcomes between male and female individuals in viral and bacterial infections, post-acute infection syndromes and vaccine responses throughout the lifespan. Understanding these sex-specific immune mechanisms represents a critical frontier for developing novel therapeutic targets and advancing personalized medicine. Klein et al. review sex differences in immune responses to viruses, bacteria and vaccines.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 4","pages":"660-673"},"PeriodicalIF":27.6,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147578319","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":"Solving the puzzle of CD8 T cell positive selection","authors":"Juan Carlos Zúñiga-Pflücker, Anton Dobrin","doi":"10.1038/s41590-026-02476-9","DOIUrl":"10.1038/s41590-026-02476-9","url":null,"abstract":"A study shows that the unique pMHC repertoire of cortical thymic epithelial cells is crucial for the differentiation of cytotoxic CD8+ T cells, providing the TCR signaling disruption needed as thymocytes move into the medulla, where a different pMHC set is encountered.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 4","pages":"652-653"},"PeriodicalIF":27.6,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147578320","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":"Author Correction: Circadian circuits control plasticity of group 3 innate lymphoid cells by sustaining epigenetic configuration of RORγt.","authors":"Bishan Bhattarai, Alina Ulezko Antonova, Jose L Fachi, Leone S Hopkins, Matthew V D McCullen, Ankita Saini, Sarah de Oliveira, Wandy L Beatty, Erik S Musiek, Vijay K Kuchroo, Mitchell A Lazar, Eugene M Oltz, Marco Colonna","doi":"10.1038/s41590-026-02507-5","DOIUrl":"https://doi.org/10.1038/s41590-026-02507-5","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147531095","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":"ZFP148 is a transcriptional repressor of cytolytic effector CD8+ T cell differentiation","authors":"Tong Xiao, Xingyu Chen, No-Joon Song, Ryan J. Brown, Anjun Ma, Jay K. Mandula, Amir Yousif, Yi Wang, Minh Quynh May Le, Jianying Li, Fengxia Gao, Bella Weaver, Heng-Yi Chen, Fang-Yun Lay, Debasish Sundi, Maria Velegraki, Payton Weltge, Juanita L. Merchant, Mark P. Rubinstein, Kenneth J. Oestreich, Chan-Wang Jerry Lio, Hazem E. Ghoneim, Xue Li, Dan Theodorescu, Gang Xin, Qin Ma, Weiguo Cui, Zihai Li","doi":"10.1038/s41590-026-02461-2","DOIUrl":"10.1038/s41590-026-02461-2","url":null,"abstract":"Progenitor CD8+ T cells differentiate into effector and exhausted progenies during chronic antigen stimulation; however, mechanisms that restrain exhaustion and sustain effector differentiation remain incompletely defined. Here we identified the transcription factor ZFP148 as a repressor of CD8+ T cell effector differentiation. ZFP148-deficient CD8+ T cells displayed increased frequency of cytolytic effector cells and reduced frequency of exhausted cells compared with Zfp148fl/fl controls during chronic viral infection. Mechanistically, ZFP148 limited the chromatin accessibility of effector-driving transcription factor motifs and directly repressed expression of the transcription factor KLF2. Furthermore, conditional ZFP148 ablation in CD8+ T cells synergized with programmed cell death-1 blockade to improve tumor control in syngeneic mouse models. Consistently, cancer patients with lower ZNF148 expression in tumor-infiltrating CD8+ T cells showed improved responsiveness to immunotherapies. Collectively, our study identifies ZFP148 as a transcriptional repressor of CD8+ T cell effector differentiation and highlights its therapeutic potential for enhancing antitumor immunity. Li and colleagues show that the transcription factor ZFP148 restrains the differentiation of antigen-specific CD8+ T cells toward cytolytic effector cells by repressing the expression of KLF2.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 4","pages":"827-840"},"PeriodicalIF":27.6,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41590-026-02461-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147524397","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}

{"title":"CD4+ T cell-mediated immunity protects from VSV-SUD lethal challenge in a mouse model of Sudan virus infection","authors":"Lara Kelchtermans, Katrien Geerts, Cuong Thi Pham, Vanshika Malviya, Winston Chiu, Carolien De Keyzer, Elias Broeckhoven, Johan Neyts, Susan Schlenner, Yeranddy A. Alpizar, Kai Dallmeier","doi":"10.1038/s41590-026-02478-7","DOIUrl":"https://doi.org/10.1038/s41590-026-02478-7","url":null,"abstract":"Recurring outbreaks of filoviruses, including Ebola virus and Sudan virus, threaten to cause large epidemics. No treatment or vaccine is available for Sudan virus and how protective immunity is achieved remains unknown. To unravel mechanisms contributing to protection, we used a surrogate mouse model of Sudan virus infection amenable to deep functional analysis. Mice vaccinated with a live viral vector based on live-attenuated YF17D expressing Sudan virus glycoprotein were protected against lethal challenge with a surrogate virus, a chimeric recombinant vesicular stomatitis virus expressing Sudan virus glycoprotein, despite lacking virus-neutralizing antibodies. Glycoprotein-specific humoral responses associated with antibody-mediated neutrophil phagocytosis and natural killer cell activation suggested Fcγ receptor (FcγR) effector involvement. However, protection was not compromised in FcγR-deficient mice. By contrast, targeted depletion and reconstitution experiments identified antigen-experienced interferon-γ (IFNγ)-secreting CD4+ T cells, particularly short-lived effector cells and regulatory T cells as key players for survival. Multiple complementary vaccination-induced effector mechanisms may contribute to Sudan virus immunity; however, only proliferative antigen-specific CD4+ T cells and sustained IFNγ production, orchestrating an acute antiviral response, appear required for protection.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"35 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147506138","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":"A transcriptomic microglia taxonomy across mouse and human pathologies","authors":"Chintan Chhatbar, Roman Sankowski, Michael Schulz, Takashi Shimizu, Marius Schwabenland, Ori Staszewski, Christian Scheiwe, Stefan Nessler, Katharina Borst, Anaelle Aurelie Dumas, Ella Trost, Daniel Berchtold, Wesley Brandão, Omar Mossad, Adrià Dalmau Gasull, Maximilian Frosch, Daniel Erny, Martin Diebold, Elena Guffart, Katharina Ternka, Mihaela Guranda, Janaki Manoja Vinnakota, Marina Friesen, Koliane Ouk, Inken Waltl, Michael LaMorte, Timothy R. Hammond, Giovanni Di Liberto, Ilena Vincenti, Mario Kreutzfeldt, Ibrahim T. Mughrabi, Yousef Al-Abed, Thomas Blank, Melanie Meyer-Luehmann, Yanick J. Crow, Nellwyn Hagen, Dimitry Ofengeim, Robert Zeiser, Matthias Kettwig, Jutta Gärtner, Andreas Meisel, Martin Schwemmle, Ulrich Kalinke, Jürgen Beck, Bertram Bengsch, Robert Thimme, Oleg Butovsky, Tamara Seredenina, Richard M. Ransohoff, Francisco J. Quintana, Katrin Kierdorf, Doron Merkler, Christine Stadelmann, Josef Priller, Marco Prinz","doi":"10.1038/s41590-026-02472-z","DOIUrl":"10.1038/s41590-026-02472-z","url":null,"abstract":"Single-cell studies have revealed substantial microglial diversity in development, homeostasis and disease. However, a framework enabling comparison and stratification of microglial states across contexts is needed. Here we generated an atlas of myeloid cell states by single-cell RNA sequencing more than one million central nervous system cells from more than 30 physiological and pathological conditions. This atlas enables us to establish a comprehensive taxonomy of myeloid cell states across brain disorders and related mouse models, comprising 27 superclusters and 192 clusters that are prevalent across diseases and largely conserved. We augment this taxonomic framework with spatial transcriptomics to map how immune cell states are organized within tissue and interact with their local cellular environment. Using in vivo perturbations, we also show that activation-associated microglial states are dependent on interferon and colony-stimulating factor 1 receptor signaling. Together, these findings provide a spatially aware taxonomic framework for central nervous system immune cells in health and disease. In this atlas paper, the authors provide a transcriptomic and spatial taxonomy of myeloid cells in the central nervous system of mice and humans in health and pathology.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 5","pages":"1066-1080"},"PeriodicalIF":27.6,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41590-026-02472-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147506137","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}

{"title":"Yin and yang of tumor-associated macrophages","authors":"","doi":"10.1038/s41590-026-02486-7","DOIUrl":"10.1038/s41590-026-02486-7","url":null,"abstract":"Our work reveals functional heterogeneity among interstitial macrophages, showing that distinct chemokine programs determine immune cell positioning and interactions within lung tumors. Interstitial macrophage niches support anti-tumor tertiary lymphoid structure formation and lymphocyte recruitment, but they also recruit pro-tumorigenic macrophages to the tumor microenvironment. Moreover, monocyte-derived dendritic cells migrate to tumor-draining lymph nodes, where they prime immunosuppressive responses. Blockade of this migration improved dendritic cell-based vaccination.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 4","pages":"658-659"},"PeriodicalIF":27.6,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147506808","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":"MHC class I on target cells regulates CD4+ T cell-mediated immunity","authors":"Emma Lauder, Mahnoor Gondal, Meng-Chih Wu, Akira Yamamoto, Laure Maneix, Dongchang Zhao, Yaping Sun, Marcin Cieslik, Arul M. Chinnaiyan, Pavan Reddy","doi":"10.1038/s41590-026-02480-z","DOIUrl":"10.1038/s41590-026-02480-z","url":null,"abstract":"Major histocompatibility complex (MHC) class I and class II molecules present antigens to CD8+ and CD4+ T cells respectively. Here we uncover a previously unrecognized role for MHC class I in modulating CD4+ T cell-mediated immunity. In allogeneic graft-versus-host disease and tumor models, we demonstrate that the absence of MHC class I on target cells significantly increases their susceptibility to CD4+ T cell cytotoxicity. Transcriptomic and functional studies suggest that this was because of heightened sensitivity to enhanced ferroptosis of the target cells. In large human transcriptomic and sequencing datasets, a role for CD4+ T cells in enhancing immune checkpoint blocker-mediated responses in persons with melanoma and mismatch-repair-deficient colon cancers that have downregulated MHC class I was suggested. These findings revise and expand the known role of MHC class I in CD8+ T cell and natural killer cell immunity and demonstrate a previously unrecognized role in CD4+ T cell-mediated cancer and alloimmunity. Here, the authors suggest that, when major histocompatibility complex class I is downregulated on allogenic or tumor cells, they are more susceptible to CD4+ T cell-mediated ferroptosis.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 5","pages":"1000-1012"},"PeriodicalIF":27.6,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41590-026-02480-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147506140","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}