Nature Immunology最新文献

{"title":"Neurons protect against fibrosis","authors":"Stephanie Houston","doi":"10.1038/s41590-025-02216-5","DOIUrl":"10.1038/s41590-025-02216-5","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 7","pages":"983-983"},"PeriodicalIF":27.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520439","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":"Maintaining immune barriers","authors":"","doi":"10.1038/s41590-025-02222-7","DOIUrl":"10.1038/s41590-025-02222-7","url":null,"abstract":"As interest in tissue-resident immunity, mucosal vaccines and host–microbiota interactions increases, barrier immunology stands at the forefront of immune defense.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 7","pages":"977-977"},"PeriodicalIF":27.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41590-025-02222-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520441","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":"FOXP3 dependence","authors":"Ioana Staicu","doi":"10.1038/s41590-025-02213-8","DOIUrl":"10.1038/s41590-025-02213-8","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 7","pages":"983-983"},"PeriodicalIF":27.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520495","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":"Train your histones","authors":"Laurie A. Dempsey","doi":"10.1038/s41590-025-02214-7","DOIUrl":"10.1038/s41590-025-02214-7","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 7","pages":"983-983"},"PeriodicalIF":27.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520442","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":"Chemosensor receptors are lipid-detecting regulators of macrophage function in cancer","authors":"Giulia Marelli, Nicolò Morina, Simone Puccio, Marta Iovino, Marta Pandini, Federica Portale, Mattia Carvetta, Divya Mishra, Elisabetta Diana, Greta Meregalli, Elvezia Paraboschi, Javier Cibella, Clelia Peano, Gianluca Basso, Gabriele De Simone, Chiara Camisaschi, Elena Magrini, Giulio Sartori, Elham Karimi, Piergiuseppe Colombo, Massimo Lazzeri, Paolo Casale, Lavinia Morosi, Giuseppe Martano, Rosanna Asselta, Eduardo Bonavita, Hiro Matsunami, Francesco Bertoni, Logan Walsh, Enrico Lugli, Diletta Di Mitri","doi":"10.1038/s41590-025-02191-x","DOIUrl":"10.1038/s41590-025-02191-x","url":null,"abstract":"Infiltration of macrophages into tumors is a hallmark of cancer progression, and re-educating tumor-associated macrophages (TAMs) toward an antitumor status is a promising immunotherapy strategy. However, the mechanisms through which cancer cells affect macrophage education are unclear, limiting the therapeutic potential of this approach. Here we conducted an unbiased genome-wide CRISPR screen of primary macrophages. Our study confirms the function of known regulators in TAM responses and reveals new insights into the behavior of these cells. We identify olfactory and vomeronasal receptors, or chemosensors, as important drivers of a tumor-supportive macrophage phenotype across multiple cancers. In vivo deletion of selected chemosensors in TAMs resulted in cancer regression and increased infiltration of tumor-reactive CD8+ T cells. In human prostate cancer tissues, palmitic acid bound to olfactory receptor 51E2 (OR51E2) expressed by TAMs, enhancing their protumor phenotype. Spatial lipidomics analysis further confirmed the presence of palmitic acid in close proximity to TAMs in prostate cancer, supporting the function of this lipid mediator in the tumor microenvironment. Overall, these data implicate chemosensors in macrophage sensing of the lipid-enriched milieu and highlight these receptors as possible therapeutic targets for enhancing antitumor immunity. Tumor-associated macrophages are pivotal in control over solid tumors. Here the authors show that these macrophages express chemosensors that detect lipid variants in the tumor microenvironment that can regulate the function of these cells.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 7","pages":"1182-1197"},"PeriodicalIF":27.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41590-025-02191-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520446","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":"Y do T cells fail","authors":"Nicholas J. Bernard","doi":"10.1038/s41590-025-02215-6","DOIUrl":"10.1038/s41590-025-02215-6","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 7","pages":"983-983"},"PeriodicalIF":27.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520440","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":"The prostacyclin receptor PTGIR is a NRF2-dependent regulator of CD8+ T cell exhaustion","authors":"Michael S. Dahabieh, Lisa M. DeCamp, Brandon M. Oswald, Susan M. Kitchen-Goosen, Zhen Fu, Matthew Vos, Shelby E. Compton, Joseph Longo, Nicole M. Foy, Kelsey S. Williams, Abigail E. Ellis, Amy Johnson, Ibukunoluwa Sodiya, Michael Vincent, Hyoungjoo Lee, Chen Yao, Tuoqi Wu, Ryan D. Sheldon, Connie M. Krawczyk, Russell G. Jones","doi":"10.1038/s41590-025-02185-9","DOIUrl":"10.1038/s41590-025-02185-9","url":null,"abstract":"CD8+ T cell exhaustion (Tex) limits immune control of cancer, but the underlying molecular drivers are unclear. In the present study, we identified the prostaglandin I2 (prostacyclin) receptor PTGIR as a cell-intrinsic regulator of T cell exhaustion. Transcriptomic profiling of terminally exhausted (Ttex) CD8+ T cells revealed increased activation of the nuclear factor erythroid 2-related factor 2 (NRF2) oxidative stress response pathway. Enhancing NRF2 activity (by conditional deletion of Kelch-like ECH-associated protein 1 (KEAP1)) boosts glutathione production in CD8+ T cells but accelerates terminal exhaustion. NRF2 upregulates PTGIR expression in CD8+ T cells. Silencing PTGIR expression enhances T cell effector function (that is, interferon-γ and granzyme production) and limits Ttex cell development in chronic infection and cancer models. Mechanistically, PTGIR signaling impairs T cell metabolism and cytokine production while inducing transcriptional features of Tex cells. These findings identify PTGIR as a NRF2-dependent immune checkpoint that regulates balance between effector and exhausted CD8+ T cell states. Targeting CD8+ T cell exhaustion is a strategy to enhance immune checkpoint inhibition and to fight cancer. Here the authors show a NRF2-dependent role for the prostaglandin I2 receptor PTGIR in controlling T cell exhaustion.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 7","pages":"1139-1151"},"PeriodicalIF":27.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41590-025-02185-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500410","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":"Lipids rewire T cell exhaustion","authors":"Marie-Elen Tuchel, Annette Oxenius","doi":"10.1038/s41590-025-02177-9","DOIUrl":"10.1038/s41590-025-02177-9","url":null,"abstract":"CD8+ T cell exhaustion and dysfunction are features of a number of diseases associated with chronic antigen exposure and in some cases can be overcome with checkpoint-blocking therapies. Researchers are now investigating the crosstalk between cellular exhaustion and metabolism with a focus on the role of lipid mediators and redox biology.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 7","pages":"984-985"},"PeriodicalIF":27.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500408","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":"Restriction of innate Tγδ17 cell plasticity by an AP-1 regulatory axis","authors":"Morgan E. Parker, Naren U. Mehta, Tzu-Chieh Liao, William H. Tomaszewski, Stephanie A. Snyder, Julia Busch, Maria Ciofani","doi":"10.1038/s41590-025-02206-7","DOIUrl":"10.1038/s41590-025-02206-7","url":null,"abstract":"Interleukin-17 (IL-17)-producing γδ T (Tγδ17) cells are innate-like mediators of intestinal barrier immunity. Although IL-17-producing helper T cell and group 3 innate lymphoid cell plasticity have been extensively studied, the mechanisms governing Tγδ17 cell effector flexibility remain undefined. Here, we combined type 3 fate mapping with single-cell ATAC-sequencing/RNA-sequencing multiome profiling to define the cellular features and regulatory networks underlying Tγδ17 cell plasticity. During homeostasis, Tγδ17 cell effector identity was stable across tissues, including for intestinal T-bet+ Tγδ17 cells that restrained interferon-γ production. However, Salmonella enterica subsp. enterica serovar Typhimurium infection induced intestinal Vγ6+ Tγδ17 cell conversion into type 1 effectors, with loss of IL-17A production and partial RORγt downregulation. Multiome analysis revealed a trajectory along Vγ6+ Tγδ17 cell effector conversion, with TIM-3 marking ex-Tγδ17 cells with enhanced type 1 functionality. Last, we characterized and validated a critical AP-1 regulatory axis centered around JUNB and FOSL2 that controls Vγ6+ Tγδ17 cell plasticity by stabilizing type 3 identity and restricting type 1 effector conversion. Ciofani and colleagues examine the plasticity of Tγδ17 cells in the gut, where they identify a role for the AP-1 transcription factors JUNB and FOSL2 in restricting type 1 plasticity.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 8","pages":"1299-1314"},"PeriodicalIF":27.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500409","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":"Microglia loss triggers glial stress and white matter damage in human leukodystrophy","authors":"","doi":"10.1038/s41590-025-02194-8","DOIUrl":"10.1038/s41590-025-02194-8","url":null,"abstract":"We show that mutations in the CSF1R gene, which cause the rare neurodegenerative disease ALSP, lead to the loss and abnormal activation of microglia. This triggers glial stress and the emergence of disease-associated oligodendrocytes with impaired myelinating potential. These findings suggest potential therapeutic strategies by modulating glial stress pathways or enhancing compensatory microglial support mechanisms.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 7","pages":"998-999"},"PeriodicalIF":27.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488379","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}