Nature Immunology最新文献

{"title":"Distinct functions of CD4+ and CD8+ regulatory T cells in autoimmunity","authors":"Ziyang Xu, Bing Su","doi":"10.1038/s41590-024-02071-w","DOIUrl":"10.1038/s41590-024-02071-w","url":null,"abstract":"Using a novel human tonsil immune organoid system, Chen et al. demonstrate that by controlling autoreactive humoral and cellular responses, human CD4+ regulatory T cells (Treg cells) and CD8+ Treg cells cooperatively restrain the otherwise uncontrolled autoimmune disease progression.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 2","pages":"159-160"},"PeriodicalIF":27.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044072","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":"ImmunOctoberfest reloaded","authors":"Anna M. Schulz, Caitlin C. Zebley, Ben Youngblood, Dietmar Zehn","doi":"10.1038/s41590-024-02069-4","DOIUrl":"10.1038/s41590-024-02069-4","url":null,"abstract":"On 23–26 September 2024, the second ImmunOctoberfest conference took place in Raitenhaslach, Germany, and brought together scientists from all over the world to catch up on recent advances in ‘Bridging Innovation and Translation in T cell Immunotherapy’.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 2","pages":"165-167"},"PeriodicalIF":27.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026717","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":"NIAID workshop on infections and autoimmune diseases","authors":"Stacy E. Ferguson, Annette L. Rothermel, Patricia Rohan, Rajeev Gautam, Deborah L. Hodge","doi":"10.1038/s41590-024-02066-7","DOIUrl":"10.1038/s41590-024-02066-7","url":null,"abstract":"On 11–12 September 2024, the National Institute of Allergy and Infectious Diseases (NIAID) convened experts to discuss associations between microorganisms and the development of autoimmune diseases.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 2","pages":"161-164"},"PeriodicalIF":27.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026718","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":"Cholesterol mobilization regulates dendritic cell maturation and the immunogenic response to cancer","authors":"Meriem Belabed, Matthew D. Park, Cédric M. Blouin, Sreekumar Balan, Chang Y. Moon, Grace Freed, Miguel Quijada-Álamo, Ante Peros, Raphaël Mattiuz, Amanda M. Reid, Nader Yatim, Jesse Boumelha, Camillia S. Azimi, Nelson M. LaMarche, Leanna Troncoso, Angelo Amabile, Jessica Le Berichel, Steven T. Chen, C. Matthias Wilk, Brian D. Brown, Kristen J. Radford, Sourav Ghosh, Carla V. Rothlin, Laurent Yvan-Charvet, Thomas U. Marron, Daniel J. Puleston, Elvin Wagenblast, Nina Bhardwaj, Christophe Lamaze, Miriam Merad","doi":"10.1038/s41590-024-02065-8","DOIUrl":"10.1038/s41590-024-02065-8","url":null,"abstract":"Maturation of conventional dendritic cells (cDCs) is crucial for maintaining tolerogenic safeguards against auto-immunity and for promoting immunogenic responses to pathogens and cancer. The subcellular mechanism for cDC maturation remains poorly defined. We show that cDCs mature by leveraging an internal reservoir of cholesterol (harnessed from extracellular cell debris and generated by de novo synthesis) to assemble lipid nanodomains on cell surfaces of maturing cDCs, enhance expression of maturation markers and stabilize immune receptor signaling. This process is dependent on cholesterol transport through Niemann–Pick disease type C1 (NPC1) and mediates homeostatic and Toll-like receptor (TLR)-induced maturation. Importantly, we identified the receptor tyrosine kinase AXL as a regulator of the NPC1-dependent construction of lipid nanodomains. Deleting AXL from cDCs enhances their maturation, thus improving anti-tumor immunity. Altogether, our study presents new insights into cholesterol mobilization as a fundamental basis for cDC maturation and highlights AXL as a therapeutic target for modulating cDCs. To mature, dendritic cells collect and synthesize cholesterol to construct lipid nanodomains on their membranes. Obstructing this process impairs their ability to prime T cells.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 2","pages":"188-199"},"PeriodicalIF":27.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990660","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":"Variants and vaccines impact nasal immunity over three waves of SARS-CoV-2","authors":"Jaclyn M. L. Walsh, Vincent N. Miao, Anna H. Owings, Ying Tang, Joshua D. Bromley, Samuel W. Kazer, Kyle Kimler, Chelsea Asare, Carly G. K. Ziegler, Samira Ibrahim, Tasneem Jivanjee, Micayla George, Andrew W. Navia, Riley S. Drake, Adam Parker, Benjamin C. Billingsley, Paul Dotherow, Spurthi Tarugu, Sai K. Kota, Hannah Laird, T. Grant Wichman, Yesenia T. Davis, Neha S. Dhaliwal, Yilianys Pride, Yanglin Guo, Michal Senitko, Jessie Harvey, John T. Bates, Gill Diamond, Michael R. Garrett, D. Ashley Robinson, I. J. Frame, Jonathan J. Lyons, Tanya O. Robinson, Alex K. Shalek, Bruce H. Horwitz, Sarah C. Glover, Jose Ordovas-Montanes","doi":"10.1038/s41590-024-02052-z","DOIUrl":"10.1038/s41590-024-02052-z","url":null,"abstract":"Viral variant and host vaccination status impact infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yet how these factors shift cellular responses in the human nasal mucosa remains uncharacterized. We performed single-cell RNA sequencing (scRNA-seq) on nasopharyngeal swabs from vaccinated and unvaccinated adults with acute Delta and Omicron SARS-CoV-2 infections and integrated with data from acute infections with ancestral SARS-CoV-2. Patients with Delta and Omicron exhibited greater similarity in nasal cell composition driven by myeloid, T cell and SARS-CoV-2hi cell subsets, which was distinct from that of ancestral cases. Delta-infected samples had a marked increase in viral RNA, and a subset of PER2+EGR1+GDF15+ epithelial cells was enriched in SARS-CoV-2 RNA+ cells in all variants. Prior vaccination was associated with increased frequency and activation of nasal macrophages. Expression of interferon-stimulated genes negatively correlated with coronavirus disease 2019 (COVID-19) severity in patients with ancestral and Delta but not Omicron variants. Our study defines nasal cell responses and signatures of disease severity across SARS-CoV-2 variants and vaccination. Ordovas-Montanes and colleagues describe the composition of the nasal cellular ecosystem and signatures of disease severity in vaccinated and unvaccinated adults during infection with the ancestral, Delta and Omicron variants of SARS-CoV-2.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 2","pages":"294-307"},"PeriodicalIF":27.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989762","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":"IRE1α–XBP1 moonlighting to restrict leukemia","authors":"Stephanie Z. Xie","doi":"10.1038/s41590-024-02061-y","DOIUrl":"10.1038/s41590-024-02061-y","url":null,"abstract":"IRE1α–XBP1 safeguards hematopoietic stem and progenitor cells by repressing pro-leukemogenic programs, independent of the unfolded protein response. A treatment strategy for acute myeloid leukemia could involve activation of the IRE1α–XBP1 axis to suppress WNT/β-catenin signaling.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 2","pages":"157-158"},"PeriodicalIF":27.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987478","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":"Intestinal microbiome metabolites control sepsis outcome","authors":"Carolina M. Polonio, Francisco J. Quintana","doi":"10.1038/s41590-024-02050-1","DOIUrl":"10.1038/s41590-024-02050-1","url":null,"abstract":"Sepsis results from a dysregulated immune response to infection. A study now shows that gut microbiota-derived metabolites prevent infection-triggered immunopathology by activating the aryl hydrocarbon receptor; pathogens inhibit this protective mechanism.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 2","pages":"155-156"},"PeriodicalIF":27.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987477","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 cocktail of kinase inhibitors that enhance the antitumor effects of CAR-T cell therapy","authors":"","doi":"10.1038/s41590-024-02049-8","DOIUrl":"10.1038/s41590-024-02049-8","url":null,"abstract":"In an unbiased high-throughput screen of 800 kinase inhibitors, we identified a cocktail of kinase inhibitors that increase the frequency of T memory stem cells for CAR-T cell therapy, resulting in improved antitumor effects both in vitro and in mouse models.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 2","pages":"170-171"},"PeriodicalIF":27.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986806","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: Dual blockade of IL-10 and PD-1 leads to control of SIV viral rebound following analytical treatment interruption","authors":"Susan Pereira Ribeiro, Zachary Strongin, Hugo Soudeyns, Felipe ten-Caten, Khader Ghneim, Gabriela Pacheco Sanchez, Giuliana Xavier de Medeiros, Perla Mariana Del Rio Estrada, Adam-Nicolas Pelletier, Timothy Hoang, Kevin Nguyen, Justin Harper, Sherrie Jean, Chelsea Wallace, Robert Balderas, Jeffrey D. Lifson, Gopalan Raghunathan, Eric Rimmer, Cinthia V. Pastuskovas, Guoxin Wu, Luca Micci, Ruy M. Ribeiro, Chi Ngai Chan, Jacob D. Estes, Guido Silvestri, Daniel M. Gorman, Bonnie J. Howell, Daria J. Hazuda, Mirko Paiardini, Rafick P. Sekaly","doi":"10.1038/s41590-025-02079-w","DOIUrl":"10.1038/s41590-025-02079-w","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 3","pages":"524-524"},"PeriodicalIF":27.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-025-02079-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986805","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":"Differential roles of human CD4+ and CD8+ regulatory T cells in controlling self-reactive immune responses","authors":"Xin Chen, Mustafa Ghanizada, Vamsee Mallajosyula, Elsa Sola, Robson Capasso, Karan Raj Kathuria, Mark M. Davis","doi":"10.1038/s41590-024-02062-x","DOIUrl":"10.1038/s41590-024-02062-x","url":null,"abstract":"Here we analyzed the relative contributions of CD4+ regulatory T cells expressing Forkhead box protein P3 (FOXP3) and CD8+ regulatory T cells expressing killer cell immunoglobulin-like receptors to the control of autoreactive T and B lymphocytes in human tonsil-derived immune organoids. FOXP3 and GZMB respectively encode proteins FOXP3 and granzyme B, which are critical to the suppressive functions of CD4+ and CD8+ regulatory T cells. Using CRISPR–Cas9 gene editing, we were able to achieve a reduction of ~90–95% in the expression of these genes. FOXP3 knockout in tonsil T cells led to production of antibodies against a variety of autoantigens and increased the affinity of influenza-specific antibodies. By contrast, GZMB knockout resulted in an increase in follicular helper T cells, consistent with the ablation of CD8+ regulatory T cells observed in mouse models, and a marked expansion of autoreactive CD8+ and CD4+ T cells. These findings highlight the distinct yet complementary roles of CD8+ and CD4+ regulatory T cells in regulating cellular and humoral responses to prevent autoimmunity. Here the authors use a tonsil organoid culture model system to investigate the roles of human CD4+ and CD8+ regulatory T cells in controlling self-reactive immune responses. CD4+ regulatory T cells were stronger regulators of autoreactive B cells, autoantibodies and antigen-specific antibody affinity, whereas CD8+ regulatory T cells predominantly controlled expansion of follicular helper cells and autoreactive CD4+ and CD8+ T cells.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 2","pages":"230-239"},"PeriodicalIF":27.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-02062-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968272","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}