Nature Immunology最新文献

{"title":"Innate immune imprints shape HIV-1 reservoir cell persistence during long-term antiretroviral therapy","authors":"Toong Seng Tan, WeiWei Sun, Ce Gao, Mathias Viard, Lucy C. Walters, Melanie Lancien, Yuko Yuki, Tram N. Van, Carlos Casquero, Xuan Guo, Rebecca Hoh, David W. Haas, Nelson Michael, Gregory D. Kirk, George Yendewa, Rajesh T. Gandhi, Seble G. Kassaye, Phyllis C. Tien, Bruce D. Walker, Michael J. Peluso, Jeffrey M. Jacobson, Steven G. Deeks, Mary Carrington, Xu G. Yu, Mathias Lichterfeld","doi":"10.1038/s41590-026-02637-w","DOIUrl":"10.1038/s41590-026-02637-w","url":null,"abstract":"Host immune responses that can target and eliminate HIV-1 reservoir cells during suppressive antiretroviral therapy are poorly understood. Here, analyzing over 6,000 proviral DNA amplicons from 104 individuals on long-term antiretroviral therapy, we found that carriers of HLA-C2 allotypes, which promote NK cell education via interactions with KIR2DL1, exhibited lower frequencies of intact proviruses. No protective effects of HLA-C2 alleles were observed during untreated infection, suggesting a selective vulnerability of reservoir cells to NK-cell-mediated immune activity under antiretroviral therapy. Supporting this, frequencies of KIR2DL1+ NK cells, particularly those coexpressing the activating HLA-E receptor NKG2C, were inversely correlated with frequencies of intact proviruses. Moreover, viral protein U variants that strongly downregulate HLA-C, increasing a missing-self response by KIR2DL1+ NK cells, were associated with smaller reservoirs in carriers of HLA-C2. Infected cells surviving long-term displayed elevated HLA-C expression, consistent with in vivo selection for resistance to KIR2DL1+ NK-cell-mediated immune clearance. Immune activity of KIR2DL1+ NK cells against viral reservoir cells was enhanced by NKG2C–HLA-E interactions, as sequence variants in HLA-E-restricted HIV-1 epitopes reduced NKG2C-dependent NK cell activation and were associated with higher frequencies of intact proviruses. These findings underscore the critical influence of host and viral genetic variation on reservoir persistence and highlight opportunities for leveraging innate immunity in HIV cure strategies. HIV reservoir cells are traditionally considered invisible to host immune responses due to viral latency. This work challenges this view by demonstrating that HIV persistence during long-term antiretroviral therapy is strongly influenced by KIR2DL1-educated NK cells.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 10","pages":"2029-2042"},"PeriodicalIF":26.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41590-026-02637-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148875282","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":"Natural killers blast HIV reservoir landscape","authors":"Daniel A. Armendariz, Valter Silva Monteiro, Ya-Chi Ho","doi":"10.1038/s41590-026-02635-y","DOIUrl":"10.1038/s41590-026-02635-y","url":null,"abstract":"Natural killer (NK) cells leave distinct footprints on the HIV reservoir, leading to a smaller HIV reservoir size in individuals carrying the HLA-C2 allele. HIV escapes NK cell-mediated immunity through mutations in the viral proteins Vpu, Gag and Env.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 10","pages":"1-3"},"PeriodicalIF":26.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148875372","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":"Immune-mediated rheumatoid arthritis: from single-cell genomics to new therapies","authors":"Lionel B. Ivashkiv","doi":"10.1038/s41590-026-02639-8","DOIUrl":"10.1038/s41590-026-02639-8","url":null,"abstract":"The recent application of single-cell genomics to the investigation of immune-mediated arthritis has resulted in an explosion of information, including the discovery of lymphocyte, myeloid and fibroblast cell subsets proposed to be pathogenic. A challenge in the field is how to leverage these exciting but largely descriptive and correlative datasets to gain insights into causality and mechanisms of disease. In this Perspective, I describe emerging data and discuss ideas about how spatial transcriptomics, ex vivo mechanistic and organoid studies, and improved use of animal models based on human disease data can advance the understanding of immune-mediated arthritis pathogenesis, with a focus on rheumatoid arthritis. These insights can form the basis for designing new therapeutic strategies and implementing clinical trials. The concepts and approaches described here for arthritis may have broader applicability to other tissues and immune-mediated diseases. Ivashkiv discusses recent advances in rheumatoid arthritis research using state-of-the-art single-cell and spatial transcriptomics and organoid systems, and discusses how these insights can be leveraged to further delineate disease biology and therapeutic opportunities.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 10","pages":"1996-2005"},"PeriodicalIF":26.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866062","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":"Good neighbors make lasting memory","authors":"Mohammad Heidarian, Vladimir P. Badovinac","doi":"10.1038/s41590-026-02645-w","DOIUrl":"10.1038/s41590-026-02645-w","url":null,"abstract":"A population of inflammatory monocytes differentiates into persistent lung-resident Gal-1+ myeloid cells that colocalize with and support the long-term maintenance and recall responses of influenza virus-induced tissue-resident memory CD8+ T cells.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 10","pages":"1983-1985"},"PeriodicalIF":26.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865982","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":"Monocyte-derived galectin-1hi cells provide innate immune help in the generation of functional memory CD8+ T cells","authors":"Kihong Lim, Ankit Dahal, Xiurui Lv, Kyun-Do Kim, Blake A. Evans, Herman Li, Laurie A. Steiner, Minsoo Kim","doi":"10.1038/s41590-026-02638-9","DOIUrl":"10.1038/s41590-026-02638-9","url":null,"abstract":"After viral infections, tissue-resident memory T cells (TRM cells) are generated and reactivated rapidly upon re-exposure to previously encountered viral pathogens, providing immediate immune effector functions to limit infection at the site of viral entry. Here we found that a subset of newly recruited CCR2+ monocytes differentiated into memory-stage CCR2-tdTomato+ cells and persisted in the lung for more than 4 months after infection with the influenza virus. Selective depletion of the memory-stage CCR2-tdTomato+ cells reduced significantly the formation of lung CD8+ TRM cells and compromised secondary heterosubtypic immune protection. Memory-stage CCR2-tdTomato+ cells colocalized with lung CD8+ TRM cells and secreted galectin-1, which activated CD8+ T cells directly and enhanced transforming growth factor-β sensing. Intranasal administration of recombinant galectin-1 as an adjuvant for the influenza vaccine induced superior memory CD8+ T cell responses. Thus, the presence of a unique memory-like monocyte-derived subset provided crucial signals to establish and maintain functional CD8+ TRM cells in the lung. Kim and colleagues describe a population of monocyte-derived lung galectin-1+ myeloid cells that support the generation and maintenance of lung-resident memory CD8+ T cells following influenza virus infection.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 10","pages":"2102-2116"},"PeriodicalIF":26.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866052","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: Short IL-18 generated by caspase-3 cleavage mobilizes NK cells to suppress tumor growth","authors":"Junchen Shen, Yu Zhang, Wenbo Tang, Mingxia Yang, Tong Cheng, Yihui Chen, Shi Yu, Qiuhong Guo, Limin Cao, Xun Wang, Hui Xiao, Lanfeng Wang, Chengyuan Wang, Chen-Ying Liu, Guangxun Meng","doi":"10.1038/s41590-026-02662-9","DOIUrl":"10.1038/s41590-026-02662-9","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 10","pages":"1-1"},"PeriodicalIF":26.5,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41590-026-02662-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148830765","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":"ID2 secures cDC1 specification by antagonizing E proteins at a pleiotropic Zeb2 enhancer","authors":"Feiya Ou, Tian-Tian Liu, Siling Du, Jing Chen, Magdalena Kraft, Giri Nam, Bishan Bhattarai, Hyeyoon Shin, Alyssa R. Koch, Theresa L. Murphy, Kenneth M. Murphy","doi":"10.1038/s41590-026-02632-1","DOIUrl":"10.1038/s41590-026-02632-1","url":null,"abstract":"The transcriptional regulator ID2 is required for type 1 classical dendritic cell (cDC1) specification, yet the mechanism has remained obscure. We previously identified the Zeb2 −165-kb enhancer as key to normal hematopoiesis, controlled by competing CEBP and NFIL3 inputs during myeloid dendritic cell divergence. Here we uncover an unprecedented role for E proteins in myelopoiesis and demonstrate that ID2 promotes cDC1 development by antagonizing E protein activity at E-boxes within the Zeb2 enhancer. Deleting these E-boxes abolishes B cell and plasmacytoid dendritic cell development while skewing myelopoiesis toward cDC1s. Remarkably, E-box deletion rescues cDC1 development in Id2-deficient mice. These findings support a two-step model in which NFIL3 transiently represses Zeb2, followed by ID2-mediated inhibition of E proteins to stabilize cDC1 fate specification. Further, this work defines a paradigm of ‘site-specific pleiotropy’, wherein distinct transcription factor motifs—E-boxes and CEBP sites—within a single enhancer direct diverse cell fates. Murphy and colleagues report that the transcriptional regulator ID2 promotes cDC1 fate specification by antagonizing E protein activity at E-boxes within the Zeb2 enhancer and establish the Zeb2 −165-kb enhancer as a pleiotropic enhancer.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 10","pages":"2043-2057"},"PeriodicalIF":26.5,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818945","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 effects","authors":"Ioana Staicu","doi":"10.1038/s41590-026-02649-6","DOIUrl":"10.1038/s41590-026-02649-6","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 9","pages":"1772-1772"},"PeriodicalIF":26.5,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811359","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":"Aging by impaired efferocytosis","authors":"Stephanie Houston","doi":"10.1038/s41590-026-02647-8","DOIUrl":"10.1038/s41590-026-02647-8","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 9","pages":"1772-1772"},"PeriodicalIF":26.5,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811358","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":"Breg cells to the rescue","authors":"Laurie A. Dempsey","doi":"10.1038/s41590-026-02648-7","DOIUrl":"10.1038/s41590-026-02648-7","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"27 9","pages":"1772-1772"},"PeriodicalIF":26.5,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811360","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}