Nature Immunology最新文献

{"title":"Recruiting lymphocytes","authors":"Laurie A. Dempsey","doi":"10.1038/s41590-025-02085-y","DOIUrl":"10.1038/s41590-025-02085-y","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 2","pages":"149-149"},"PeriodicalIF":27.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071397","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":"Exhaustion is planned","authors":"Nicholas J. Bernard","doi":"10.1038/s41590-025-02084-z","DOIUrl":"10.1038/s41590-025-02084-z","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 2","pages":"149-149"},"PeriodicalIF":27.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071458","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":"Progressively differentiated TFH13 cells are stabilized by JunB to mediate allergen germinal center responses","authors":"Pragya Chandrakar, Cody S. Nelson, Manuel A. Podestà, Cecilia B. Cavazzoni, Maya Gempler, Jeong-Mi Lee, Sierra Richardson, Hengcheng Zhang, Snigdha Samarpita, Maria Ciofani, Talal Chatila, Vijay K. Kuchroo, Peter T. Sage","doi":"10.1038/s41590-025-02077-y","DOIUrl":"10.1038/s41590-025-02077-y","url":null,"abstract":"Allergic diseases are common and affect a large proportion of the population. Interleukin-13 (IL-13)-expressing follicular helper T (TFH13) cells are a newly identified population of TFH cells that have been associated with high-affinity IgE responses. However, the origins, developmental signals, transcriptional programming and precise functions of TFH13 cells are unknown. Here, we examined the developmental signals for TFH13 cells and found a direct and progressive differentiation pathway marked by the production of IL-21. These two pathways differed in kinetics and extrinsic requirements. However, both pathways converged, forming transcriptionally similar TFH13 cells that express the transcription factor JunB as a critical stabilizing factor. Using an intersectional genetics-based TFH13-diphtheria toxin receptor model to perturb these cells, we found that TFH13 cells were essential to drive broad germinal center responses and allergen-specific IgG and IgE. Moreover, we found that IL-21 is a broad positive regulator of allergen germinal center B cells and synergizes with IL-13 produced by TFH13 cells to amplify allergic responses. Thus, TFH13 cells orchestrate multiple features of allergic inflammation. TFH cells that express IL-13 are associated with high-affinity IgE responses, but factors controlling their development, transcriptional programming and exact function have remained unclear. Here, Chandrakar et al. find that the transcription factor JunB is required for TFH13 cell maintenance and that TFH13 cells producing IL-21 drive broad germinal center responses to allergen-specific IgG and IgE.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 3","pages":"473-483"},"PeriodicalIF":27.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071408","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":"Single-cell profiling of the immune landscape across the human lifespan","authors":"","doi":"10.1038/s41590-024-02058-7","DOIUrl":"10.1038/s41590-024-02058-7","url":null,"abstract":"Using a combination of single-cell RNA sequencing, T cell and B cell receptor sequencing, and mass cytometry analyses, we characterized the dynamics of peripheral immune cells across the human lifespan. Based on this resource, we present a single-cell immune aging clock to assess an individual’s immune status across different life stages.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 2","pages":"172-173"},"PeriodicalIF":27.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055065","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":"Integrating single-cell RNA and T cell/B cell receptor sequencing with mass cytometry reveals dynamic trajectories of human peripheral immune cells from birth to old age","authors":"Yufei Wang, Ronghong Li, Renyang Tong, Taiwei Chen, Mingze Sun, Lingjie Luo, Zheng Li, Yifan Chen, Yichao Zhao, Chensheng Zhang, Lin Wei, Wei Lin, Haoyan Chen, Kun Qian, Alex F. Chen, Junling Liu, Lei Chen, Bin Li, Feng Wang, Li Wang, Bing Su, Jun Pu","doi":"10.1038/s41590-024-02059-6","DOIUrl":"10.1038/s41590-024-02059-6","url":null,"abstract":"A comprehensive understanding of the evolution of the immune landscape in humans across the entire lifespan at single-cell transcriptional and protein levels, during development, maturation and senescence is currently lacking. We recruited a total of 220 healthy volunteers from the Shanghai Pudong Cohort (NCT05206643), spanning 13 age groups from 0 to over 90 years, and profiled their peripheral immune cells through single-cell RNA-sequencing coupled with single T cell and B cell receptor sequencing, high-throughput mass cytometry, bulk RNA-sequencing and flow cytometry validation experiments. We revealed that T cells were the most strongly affected by age and experienced the most intensive rewiring in cell–cell interactions during specific age. Different T cell subsets displayed different aging patterns in both transcriptomes and immune repertoires; examples included GNLY+CD8+ effector memory T cells, which exhibited the highest clonal expansion among all T cell subsets and displayed distinct functional signatures in children and the elderly; and CD8+ MAIT cells, which reached their peaks of relative abundance, clonal diversity and antibacterial capability in adolescents and then gradually tapered off. Interestingly, we identified and experimentally verified a previously unrecognized ‘cytotoxic’ B cell subset that was enriched in children. Finally, an immune age prediction model was developed based on lifecycle-wide single-cell data that can evaluate the immune status of healthy individuals and identify those with disturbed immune functions. Our work provides both valuable insights and resources for further understanding the aging of the immune system across the whole human lifespan. In this Resource, authors profile peripheral immune cells from a total of 220 healthy volunteers from birth to over 90 years. This revealed that T cells were most affected by aging with divergent aging patterns in different subsets and identified a population of cytotoxic B cells that were enriched in children.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 2","pages":"308-322"},"PeriodicalIF":27.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-02059-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055072","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":"Variant-specific local tissue response to SARS-CoV-2 in the nasal mucosa","authors":"Debbie van Baarle, Martijn C. Nawijn","doi":"10.1038/s41590-024-02067-6","DOIUrl":"10.1038/s41590-024-02067-6","url":null,"abstract":"Cell-type-specific SARS-CoV-2-induced responses in nasal mucosa differ largely between ancestral, Delta and Omicron cases, including the association with severe disease and the cellular and immunological effects of prior vaccination.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 2","pages":"152-154"},"PeriodicalIF":27.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055064","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":"Signature cytokine-associated transcriptome analysis of effector γδ T cells identifies subset-specific regulators of peripheral activation","authors":"Daniel Inácio, Tiago Amado, Ana Pamplona, Daniel Sobral, Carolina Cunha, Rita F. Santos, Liliana Oliveira, Nelly Rouquié, Alexandre M. Carmo, Renaud Lesourne, Anita Q. Gomes, Bruno Silva-Santos","doi":"10.1038/s41590-024-02073-8","DOIUrl":"10.1038/s41590-024-02073-8","url":null,"abstract":"γδ T cells producing either interleukin-17A (γδ17 cells) or interferon-γ (γδIFN cells) are generated in the mouse thymus, but the molecular regulators of their peripheral functions are not fully characterized. Here we established an Il17a-GFP:Ifng-YFP double-reporter mouse strain to analyze at unprecedented depth the transcriptomes of pure γδ17 cell versus γδIFN cell populations from peripheral lymph nodes. Within a very high fraction of differentially expressed genes, we identify a panel of 20 new signature genes in steady-state γδ17 cells versus γδIFN cells, which we further validate in models of experimental autoimmune encephalomyelitis and cerebral malaria, respectively. Among the signature genes, we show that the co-receptor CD6 and the signaling protein Themis promote the activation and proliferation of peripheral γδIFN cells in response to T cell antigen receptor stimulation in vitro and to Plasmodium infection in vivo. This resource can help to understand the distinct activities of effector γδ T cell subsets in pathophysiology. Here, the authors use a double-reporter system to tag IFNγ-producing versus IL-17A-producing γδ T cells to compile a trancriptomic resource of these cell subsets in mice at steady state and in response to cerebral malaria or multiple sclerosis.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 3","pages":"497-510"},"PeriodicalIF":27.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-02073-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055054","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":"T cell immune evasion by SARS-CoV-2 JN.1 escapees targeting two cytotoxic T cell epitope hotspots","authors":"Jinmin Tian, Bingli Shang, Jianing Zhang, Yuanyuan Guo, Min Li, Yuechao Hu, Dan Bai, Junying She, Yang Han, Peipei Guo, Mengkun Huang, Yalan Wang, Maoshun Liu, Jie Zhang, Beiwei Ye, Yaxin Guo, Mengjie Yang, Ying Lin, Ting Zhang, Xin Sun, Xiaoju Yuan, Danni Zhang, Ziqian Xu, Yan Chai, Jianxun Qi, Kefang Liu, Shuguang Tan, Yingze Zhao, Jikun Zhou, Rui Song, George F. Gao, Jun Liu","doi":"10.1038/s41590-024-02051-0","DOIUrl":"10.1038/s41590-024-02051-0","url":null,"abstract":"Although antibody escape is observed in emerging severe acute respiratory syndrome coronavirus 2 variants, T cell escape, especially after the global circulation of BA.2.86/JN.1, is unexplored. Here we demonstrate that T cell evasion exists in epitope hotspots spanning BA.2.86/JN.1 mutations. The newly emerging Q229K at this conserved nucleocapsid protein site impairs HLA-A2 epitope hotspot recognition. The association between HLA-A24 convalescents and T cell immune escape points to the spike (S) protein epitope S448–456NYNYLYRLF, with multiple mutations from Delta to JN.1, including L452Q, L452R, F456L, N450D and L452W, and N450D, L452W and L455S. A cliff drop of immune responses was observed for S448–456NYNYRYRLF (Delta/BA.5.2) and S448–456NYDYWYRSF (JN.1), but with immune preservation of S448–456NYDYWYRLF (BA.2.86). Structural analyses showed that hydrophobicity exposure determines the pronounced escape of L452R and L455S mutants, which was further confirmed by T cell receptor binding. This study highlights the characteristics and molecular mechanisms of the T cell immune escape for JN.1 and provides new insights into understanding the dominant circulation of variants, from the viewpoint of cytotoxic T cell evasion. Liu and colleagues examine how severe acute respiratory syndrome coronavirus 2 variants evade CD8+ T cell epitope recognition.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 2","pages":"265-278"},"PeriodicalIF":27.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049992","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":"Robust mucosal SARS-CoV-2-specific T cells effectively combat COVID-19 and establish polyfunctional resident memory in patient lungs","authors":"Airu Zhu, Zhao Chen, Qihong Yan, Mei Jiang, Xuesong Liu, Zhengtu Li, Na Li, Chunli Tang, Wenhua Jian, Jiangping He, Lan Chen, Jinling Cheng, Canjie Chen, Tian Tang, Zhiwei Xu, Qingtao Hu, Fang Li, Yanqun Wang, Jing Sun, Zhen Zhuang, Liyan Wen, Jianfen Zhuo, Donglan Liu, Yanjun Zhang, Xiaofang Huang, Suxiang Li, Qiuhui Zeng, Fangli Chen, Liang Zhou, Dongdong Liu, Changhao Zhong, Yu Chen, Shiyue Li, Kangli Liang, Na Zhong, Xinmei Zhang, Jiekai Chen, Xiaobo Chen, Yonghao Xu, Nanshan Zhong, Jingxian Zhao, Jincun Zhao","doi":"10.1038/s41590-024-02072-9","DOIUrl":"10.1038/s41590-024-02072-9","url":null,"abstract":"Mucosal antigen-specific T cells are pivotal for pathogen clearance and immune modulation in respiratory infections. Dysregulated T cell responses exacerbate coronavirus disease 2019 severity, marked by cytokine storms and respiratory failure. Despite extensive description in peripheral blood, the characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells in the lungs remain elusive. Here we conducted integrated single-cell profiling of SARS-CoV-2-specific T cells in 122 bronchoalveolar lavage fluid (BALF) and 280 blood samples from 159 patients, including 27 paired BALF and blood samples from 24 patients. SARS-CoV-2-specific T cells were robustly elicited in BALF irrespective of prior vaccination, correlating with diminished viral loads, lessened systemic inflammation and improved respiratory function. SARS-CoV-2-specific T cells in BALF exhibited profound activation, along with proliferative and multi-cytokine-producing capabilities and a glycolysis-driven metabolic signature, which were distinct from those observed in peripheral blood mononuclear cells. After viral clearance, these specific T cells maintained a polyfunctional tissue-resident memory phenotype, highlighting their critical roles in infection control and long-term protection. The authors show that SARS-CoV-2-specific T cells in the lung are key to fighting infection and persist after viral clearance, contributing to long-term immunity and protection.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 3","pages":"459-472"},"PeriodicalIF":27.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-02072-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049991","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":"Evasion of T cell responses by newly emerging SARS-CoV-2 variants","authors":"","doi":"10.1038/s41590-024-02053-y","DOIUrl":"10.1038/s41590-024-02053-y","url":null,"abstract":"We describe how newly emerging mutations in the SARS-CoV-2 variant BA.2.86 sub-variant JN.1 contribute to evasion of CD8+ T cell responses. Mutations occurring in T cell epitope hotspots in the viral spike protein and in a highly conserved site in the viral nucleocapsid suggest that T cell-mediated immune pressure is a key driving force for SARS-CoV-2 evolution and adaptation.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 2","pages":"168-169"},"PeriodicalIF":27.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049990","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}