Nature Immunology最新文献_第8页

Recasting resistance to Mycobacterium tuberculosis 重塑结核分枝杆菌的抗药性。

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-07-24 DOI: 10.1038/s41590-024-01907-9

Jason R. Andrews

引用次数: 0

Dietary glutamine supports mucosal germinal center B cell lymphomas 膳食谷氨酰胺对粘膜生殖中心 B 细胞淋巴瘤有支持作用

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-07-22 DOI: 10.1038/s41590-024-01911-z

引用次数: 0

Immunological imprinting and risks of influenza B virus infection 免疫印记与感染乙型流感病毒的风险

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-07-19 DOI: 10.1038/s41590-024-01906-w

Isaac C. L. Chow, Sook-San Wong

引用次数: 0

T cell dysfunction and therapeutic intervention in cancer 癌症中的 T 细胞功能障碍和治疗干预。

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-07-18 DOI: 10.1038/s41590-024-01896-9

Caitlin C. Zebley, Dietmar Zehn, Stephen Gottschalk, Hongbo Chi

{"title":"T cell dysfunction and therapeutic intervention in cancer","authors":"Caitlin C. Zebley, Dietmar Zehn, Stephen Gottschalk, Hongbo Chi","doi":"10.1038/s41590-024-01896-9","DOIUrl":"10.1038/s41590-024-01896-9","url":null,"abstract":"Recent advances in immunotherapy have affirmed the curative potential of T cell-based approaches for treating relapsed and refractory cancers. However, the therapeutic efficacy is limited in part owing to the ability of cancers to evade immunosurveillance and adapt to immunological pressure. In this Review, we provide a brief overview of cancer-mediated immunosuppressive mechanisms with a specific focus on the repression of the surveillance and effector function of T cells. We discuss CD8+ T cell exhaustion and functional heterogeneity and describe strategies for targeting the molecular checkpoints that restrict T cell differentiation and effector function to bolster immunotherapeutic effects. We also delineate the emerging contributions of the tumor microenvironment to T cell metabolism and conclude by highlighting discovery-based approaches for developing future cellular therapies. Continued exploration of T cell biology and engineering hold great promise for advancing therapeutic interventions for cancer. In this Review, the authors analyze functional and dysfunctional T cell features to make sense of cancer immunotherapy efficacy and how to improve it.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723960","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}

引用次数: 0

Gα13 restricts nutrient driven proliferation in mucosal germinal centers Gα13 限制了粘膜生殖中心的营养驱动增殖。

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-07-18 DOI: 10.1038/s41590-024-01910-0

Hang T. Nguyen, Moyi Li, Rahul Vadakath, Keirstin A. Henke, Tam C. Tran, Huifang Li, Maryam Yamadi, Sriranjani Darbha, Yandan Yang, Juraj Kabat, Anne R. Albright, Enoc Granados Centeno, James D. Phelan, Sandrine Roulland, Da Wei Huang, Michael C. Kelly, Ryan M. Young, Stefania Pittaluga, Simone Difilippantonio, Jagan R. Muppidi

{"title":"Gα13 restricts nutrient driven proliferation in mucosal germinal centers","authors":"Hang T. Nguyen, Moyi Li, Rahul Vadakath, Keirstin A. Henke, Tam C. Tran, Huifang Li, Maryam Yamadi, Sriranjani Darbha, Yandan Yang, Juraj Kabat, Anne R. Albright, Enoc Granados Centeno, James D. Phelan, Sandrine Roulland, Da Wei Huang, Michael C. Kelly, Ryan M. Young, Stefania Pittaluga, Simone Difilippantonio, Jagan R. Muppidi","doi":"10.1038/s41590-024-01910-0","DOIUrl":"10.1038/s41590-024-01910-0","url":null,"abstract":"Germinal centers (GCs) that form in mucosal sites are exposed to gut-derived factors that have the potential to influence homeostasis independent of antigen receptor-driven selective processes. The G-protein Gα13 confines B cells to the GC and limits the development of GC-derived lymphoma. We discovered that Gα13-deficiency fuels the GC reaction via increased mTORC1 signaling and Myc protein expression specifically in the mesenteric lymph node (mLN). The competitive advantage of Gα13-deficient GC B cells (GCBs) in mLN was not dependent on T cell help or gut microbiota. Instead, Gα13-deficient GCBs were selectively dependent on dietary nutrients likely due to greater access to gut lymphatics. Specifically, we found that diet-derived glutamine supported proliferation and Myc expression in Gα13-deficient GCBs in the mLN. Thus, GC confinement limits the effects of dietary glutamine on GC dynamics in mucosal tissues. Gα13 pathway mutations coopt these processes to promote the gut tropism of aggressive lymphoma. Muppidi and colleagues show that loss of Gα13 drives B cell lymphomas preferentially in the mesenteric lymph nodes. They find that Gα13 is required to counteract mTORC1 and Myc signaling that is driven by the availability of dietary glutamine.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-01910-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723959","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}

引用次数: 0

A humanized mouse that mounts specific and mature antibody and autoantibody responses 一种能产生特异性成熟抗体和自身抗体反应的人源化小鼠。

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-07-18 DOI: 10.1038/s41590-024-01908-8

引用次数: 0

Chromatin state and BACH2 control TH17 cell functional heterogeneity 染色质状态和BACH2控制TH17细胞的功能异质性

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-07-17 DOI: 10.1038/s41590-024-01904-y

引用次数: 0

Vγ9Vδ2 T cells recognize butyrophilin 2A1 and 3A1 heteromers Vγ9Vδ2 T 细胞识别丁淀粉样蛋白 2A1 和 3A1 异构体

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-07-16 DOI: 10.1038/s41590-024-01892-z

Thomas S. Fulford, Caroline Soliman, Rebecca G. Castle, Marc Rigau, Zheng Ruan, Olan Dolezal, Rebecca Seneviratna, Hamish G. Brown, Eric Hanssen, Andrew Hammet, Shihan Li, Samuel J. Redmond, Amy Chung, Michael A. Gorman, Michael W. Parker, Onisha Patel, Thomas S. Peat, Janet Newman, Andreas Behren, Nicholas A. Gherardin, Dale I. Godfrey, Adam P. Uldrich

{"title":"Vγ9Vδ2 T cells recognize butyrophilin 2A1 and 3A1 heteromers","authors":"Thomas S. Fulford, Caroline Soliman, Rebecca G. Castle, Marc Rigau, Zheng Ruan, Olan Dolezal, Rebecca Seneviratna, Hamish G. Brown, Eric Hanssen, Andrew Hammet, Shihan Li, Samuel J. Redmond, Amy Chung, Michael A. Gorman, Michael W. Parker, Onisha Patel, Thomas S. Peat, Janet Newman, Andreas Behren, Nicholas A. Gherardin, Dale I. Godfrey, Adam P. Uldrich","doi":"10.1038/s41590-024-01892-z","DOIUrl":"10.1038/s41590-024-01892-z","url":null,"abstract":"Butyrophilin (BTN) molecules are emerging as key regulators of T cell immunity; however, how they trigger cell-mediated responses is poorly understood. Here, the crystal structure of a gamma-delta T cell antigen receptor (γδTCR) in complex with BTN2A1 revealed that BTN2A1 engages the side of the γδTCR, leaving the apical TCR surface bioavailable. We reveal that a second γδTCR ligand co-engages γδTCR via binding to this accessible apical surface in a BTN3A1-dependent manner. BTN2A1 and BTN3A1 also directly interact with each other in cis, and structural analysis revealed formation of W-shaped heteromeric multimers. This BTN2A1–BTN3A1 interaction involved the same epitopes that BTN2A1 and BTN3A1 each use to mediate the γδTCR interaction; indeed, locking BTN2A1 and BTN3A1 together abrogated their interaction with γδTCR, supporting a model wherein the two γδTCR ligand-binding sites depend on accessibility to cryptic BTN epitopes. Our findings reveal a new paradigm in immune activation, whereby γδTCRs sense dual epitopes on BTN complexes. In this study, Uldrich and colleagues describe the crystal structure of the Vγ9Vδ2 T cell antigen receptor (TCR) interacting with BTN2A1 and demonstrate the existence of a second ligand that co-binds to a distinct epitope on Vγ9Vδ2 TCR. Using these data, the authors suggest a model of Vγ9Vδ2 TCR activation in which BTN2A1 and BTN3A1 are tethered to each other at the steady state, and must disengage to allow TCR binding.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141624834","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}

引用次数: 0

BACH2 regulates diversification of regulatory and proinflammatory chromatin states in TH17 cells BACH2调控TH17细胞中调控和促炎染色质状态的多样化

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-07-15 DOI: 10.1038/s41590-024-01901-1

Pratiksha I. Thakore, Alexandra Schnell, Linglin Huang, Maryann Zhao, Yu Hou, Elena Christian, Sarah Zaghouani, Chao Wang, Vasundhara Singh, Anvita Singaraju, Rajesh Kumar Krishnan, Deneen Kozoriz, Sai Ma, Venkat Sankar, Samuele Notarbartolo, Jason D. Buenrostro, Federica Sallusto, Nikolaos A. Patsopoulos, Orit Rozenblatt-Rosen, Vijay K. Kuchroo, Aviv Regev

{"title":"BACH2 regulates diversification of regulatory and proinflammatory chromatin states in TH17 cells","authors":"Pratiksha I. Thakore, Alexandra Schnell, Linglin Huang, Maryann Zhao, Yu Hou, Elena Christian, Sarah Zaghouani, Chao Wang, Vasundhara Singh, Anvita Singaraju, Rajesh Kumar Krishnan, Deneen Kozoriz, Sai Ma, Venkat Sankar, Samuele Notarbartolo, Jason D. Buenrostro, Federica Sallusto, Nikolaos A. Patsopoulos, Orit Rozenblatt-Rosen, Vijay K. Kuchroo, Aviv Regev","doi":"10.1038/s41590-024-01901-1","DOIUrl":"10.1038/s41590-024-01901-1","url":null,"abstract":"Interleukin-17 (IL-17)-producing helper T (TH17) cells are heterogenous and consist of nonpathogenic TH17 (npTH17) cells that contribute to tissue homeostasis and pathogenic TH17 (pTH17) cells that mediate tissue inflammation. Here, we characterize regulatory pathways underlying TH17 heterogeneity and discover substantial differences in the chromatin landscape of npTH17 and pTH17 cells both in vitro and in vivo. Compared to other CD4+ T cell subsets, npTH17 cells share accessible chromatin configurations with regulatory T cells, whereas pTH17 cells exhibit features of both npTH17 cells and type 1 helper T (TH1) cells. Integrating single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) and single-cell RNA sequencing (scRNA-seq), we infer self-reinforcing and mutually exclusive regulatory networks controlling different cell states and predicted transcription factors regulating TH17 cell pathogenicity. We validate that BACH2 promotes immunomodulatory npTH17 programs and restrains proinflammatory TH1-like programs in TH17 cells in vitro and in vivo. Furthermore, human genetics implicate BACH2 in multiple sclerosis. Overall, our work identifies regulators of TH17 heterogeneity as potential targets to mitigate autoimmunity. Regulating the balance between TH17 cells that drive autoimmune inflammation and nonpathogenic TH17 cells is critical for limiting autoimmune pathology. Here, the authors extensively characterize these two cell states at the transcriptomic and epigenetic levels and show how BACH2 is protective in this context.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618203","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}

引用次数: 0

The immunology of systemic lupus erythematosus 系统性红斑狼疮的免疫学

IF 27.7 1区医学

Nature Immunology Pub Date : 2024-07-15 DOI: 10.1038/s41590-024-01898-7

George C. Tsokos

引用次数: 0