Nature Immunology最新文献

A STAT3–STING–IFN axis controls the metastatic spread of small cell lung cancer STAT3-STING-IFN 轴控制小细胞肺癌的转移扩散

IF 30.5 1区医学

Nature Immunology Pub Date : 2024-11-21 DOI: 10.1038/s41590-024-02014-5

Aleks C. Guanizo, Quinton Luong, W. Samantha N. Jayasekara, Eveline D. de Geus, Chaitanya Inampudi, Vincent Senyang Xue, Jasmine Chen, Nicole A. de Weerd, Antony Y. Matthews, Michael P. Gantier, Jesse J. Balic, Surein Arulananda, Daniel J. Garama, Paul J. Hertzog, Vinod Ganju, D. Neil Watkins, Jason E. Cain, Daniel J. Gough

{"title":"A STAT3–STING–IFN axis controls the metastatic spread of small cell lung cancer","authors":"Aleks C. Guanizo, Quinton Luong, W. Samantha N. Jayasekara, Eveline D. de Geus, Chaitanya Inampudi, Vincent Senyang Xue, Jasmine Chen, Nicole A. de Weerd, Antony Y. Matthews, Michael P. Gantier, Jesse J. Balic, Surein Arulananda, Daniel J. Garama, Paul J. Hertzog, Vinod Ganju, D. Neil Watkins, Jason E. Cain, Daniel J. Gough","doi":"10.1038/s41590-024-02014-5","DOIUrl":"https://doi.org/10.1038/s41590-024-02014-5","url":null,"abstract":"Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor characterized by a high metastatic potential with an overall survival rate of ~5%. The transcription factor signal transducer and activator of transcription 3 (STAT3) is overexpressed by >50% of tumors, including SCLC, but its role in SCLC development and metastasis is unclear. Here, we show that, while STAT3 deletion restricts primary tumor growth, it paradoxically enhances metastatic spread by promoting immune evasion. This occurs because STAT3 is crucial for maintaining the immune sensor stimulator of interferon (IFN) genes (STING). Without STAT3, the cyclic adenosine monophosphate–guanosine monophosphate synthase–STING pathway is inactive, resulting in decreased type I IFN secretion and an IFN gene signature. Importantly, restoration of IFN signaling through re-expression of endogenous STING, enforced expression of IFN response factor 7 or administration of recombinant type I IFN re-established antitumor immunity, inhibiting metastatic SCLC in vivo. These data show the potential of augmenting the innate immune response to block metastatic SCLC.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"38 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678438","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

PD-1 and CD73 on naive CD4+ T cells synergistically limit responses to self 天真 CD4+ T 细胞上的 PD-1 和 CD73 可协同限制对自身细胞的反应

IF 30.5 1区医学

Nature Immunology Pub Date : 2024-11-21 DOI: 10.1038/s41590-024-02021-6

Felix Sebastian Nettersheim, Simon Brunel, Robert S. Sinkovits, Sujit Silas Armstrong, Payel Roy, Monica Billitti, Kouji Kobiyama, Ahmad Alimadadi, Sergei Bombin, Lihui Lu, Martina Zoccheddu, Mohammad Oliaeimotlagh, Chris A. Benedict, Alessandro Sette, Klaus Ley

{"title":"PD-1 and CD73 on naive CD4+ T cells synergistically limit responses to self","authors":"Felix Sebastian Nettersheim, Simon Brunel, Robert S. Sinkovits, Sujit Silas Armstrong, Payel Roy, Monica Billitti, Kouji Kobiyama, Ahmad Alimadadi, Sergei Bombin, Lihui Lu, Martina Zoccheddu, Mohammad Oliaeimotlagh, Chris A. Benedict, Alessandro Sette, Klaus Ley","doi":"10.1038/s41590-024-02021-6","DOIUrl":"https://doi.org/10.1038/s41590-024-02021-6","url":null,"abstract":"Vaccination with self- and foreign peptides induces weak and strong expansion of antigen-specific CD4+ T cells, respectively, but the mechanism is not known. In the present study, we used computational analysis of the entire mouse major histocompatibility complex class II peptidome to test how much of the naive CD4+ T cell repertoire specific for self-antigens was shaped by negative selection in the thymus and found that negative selection only partially explained the difference between responses to self and foreign. In naive uninfected and unimmunized mice, we identified higher expression of programmed cell death protein 1 (PD-1) and CD73 mRNA and protein on self-specific CD4+ T cells compared with foreign-specific CD4+ T cells. Pharmacological or genetic blockade of PD-1 and CD73 significantly increased the vaccine-induced expansion of self-specific CD4+ T cells and their transcriptomes were similar to those of foreign-specific CD4+ T cells. We concluded that PD-1 and CD73 synergistically limited CD4+ T cell responses to self. These observations have implications for the development of tolerogenic vaccines and cancer immunotherapy.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"13 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678285","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

UBXN9 governs GLUT4-mediated spatial confinement of RIG-I-like receptors and signaling UBXN9 控制着 GLUT4 介导的 RIG-I 样受体和信号传导的空间限制

IF 30.5 1区医学

Nature Immunology Pub Date : 2024-11-20 DOI: 10.1038/s41590-024-02004-7

Andrew G. Harrison, Duomeng Yang, Jason G. Cahoon, Tingting Geng, Ziming Cao, Timofey A. Karginov, Youjia Hu, Xin Li, Conner C. Chiari, Yibing Qyang, Anthony T. Vella, Zhichao Fan, Sivapriya Kailasan Vanaja, Vijay A. Rathinam, Carol A. Witczak, Jonathan S. Bogan, Penghua Wang

{"title":"UBXN9 governs GLUT4-mediated spatial confinement of RIG-I-like receptors and signaling","authors":"Andrew G. Harrison, Duomeng Yang, Jason G. Cahoon, Tingting Geng, Ziming Cao, Timofey A. Karginov, Youjia Hu, Xin Li, Conner C. Chiari, Yibing Qyang, Anthony T. Vella, Zhichao Fan, Sivapriya Kailasan Vanaja, Vijay A. Rathinam, Carol A. Witczak, Jonathan S. Bogan, Penghua Wang","doi":"10.1038/s41590-024-02004-7","DOIUrl":"https://doi.org/10.1038/s41590-024-02004-7","url":null,"abstract":"The cytoplasmic RIG-I-like receptors (RLRs) recognize viral RNA and initiate innate antiviral immunity. RLR signaling also triggers glycolytic reprogramming through glucose transporters (GLUTs), whose role in antiviral immunity is elusive. Here, we unveil that insulin-responsive GLUT4 inhibits RLR signaling independently of glucose uptake in adipose and muscle tissues. At steady state, GLUT4 is trapped at the Golgi matrix by ubiquitin regulatory X domain 9 (UBXN9, TUG). Following RNA virus infection, GLUT4 is released and translocated to the cell surface where it spatially segregates a significant pool of cytosolic RLRs, preventing them from activating IFN-β responses. UBXN9 deletion prompts constitutive GLUT4 translocation, sequestration of RLRs and attenuation of antiviral immunity, whereas GLUT4 deletion heightens RLR signaling. Notably, reduced GLUT4 expression is uniquely associated with human inflammatory myopathies characterized by hyperactive interferon responses. Overall, our results demonstrate a noncanonical UBXN9-GLUT4 axis that controls antiviral immunity via plasma membrane tethering of cytosolic RLRs.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"99 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673219","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 diverse roles of neutrophils from protection to pathogenesis 中性粒细胞从保护到致病的多种作用

IF 30.5 1区医学

Nature Immunology Pub Date : 2024-11-20 DOI: 10.1038/s41590-024-02006-5

Rana Herro, H. Leighton Grimes

{"title":"The diverse roles of neutrophils from protection to pathogenesis","authors":"Rana Herro, H. Leighton Grimes","doi":"10.1038/s41590-024-02006-5","DOIUrl":"https://doi.org/10.1038/s41590-024-02006-5","url":null,"abstract":"Neutrophil granulocytes are the most abundant leukocytes in the blood and constitute a critical arm of innate immunity. They are generated in the bone marrow, and under homeostatic conditions enter the bloodstream to patrol tissues and scout for potential pathogens that they quickly destroy through phagocytosis, intracellular degradation, release of granules and formation of extracellular traps. Thus, neutrophils are important effector cells involved in antibacterial defense. However, neutrophils can also be pathogenic. Emerging data suggest they have critical functions related to tissue repair and fibrosis. Moreover, similarly to other innate immune cells, neutrophil cell states are affected by their microenvironment. Notably, this includes tumors that co-opt neutrophils. Neutrophils can undergo transcriptional and epigenetic reprogramming, thus causing or modulating inflammation and injury. It is also possible that distinct neutrophil subsets are generated with designated functions in the bone marrow. Understanding neutrophil plasticity and alternative cell states will help resolve their contradictive roles. This Review summarizes the most recent key findings surrounding protective versus pathogenic functions of neutrophils; elaborating on phenotype-specific subsets of neutrophils and their involvement in homeostasis and disease.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"74 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673215","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

Remodeling of Il4-Il13-Il5 locus underlies selective gene expression Il4-Il13-Il5基因座重塑是选择性基因表达的基础

IF 30.5 1区医学

Nature Immunology Pub Date : 2024-11-20 DOI: 10.1038/s41590-024-02007-4

Hiroyuki Nagashima, Justin Shayne, Kan Jiang, Franziska Petermann, Aleksandra Pękowska, Yuka Kanno, John J. O’Shea

{"title":"Remodeling of Il4-Il13-Il5 locus underlies selective gene expression","authors":"Hiroyuki Nagashima, Justin Shayne, Kan Jiang, Franziska Petermann, Aleksandra Pękowska, Yuka Kanno, John J. O’Shea","doi":"10.1038/s41590-024-02007-4","DOIUrl":"https://doi.org/10.1038/s41590-024-02007-4","url":null,"abstract":"The type 2 cytokines, interleukin (IL)-4, IL-13 and IL-5 reside within a multigene cluster. Both innate (ILC2) and adaptive T helper 2 (TH2) lymphocytes secrete type 2 cytokines with diverse production spectra. Using transcription factor footprint and chromatin accessibility, we systemically cataloged regulatory elements (REs) denoted as SHS-I/II, KHS-I/II, +6.5kbIl13, 5HS-I(a, b, c, d, e), 5HS-II and 5HS-III(a, b, c) across the extended Il4-Il13-Il5 locus in mice. Physical proximities among REs were coordinately remodeled in three-dimensional space after cell activation, leading to divergent compartmentalization of Il4, Il13 and Il5 with varied combinations of REs. Deletions of REs revealed no single RE solely accounted for selective regulation of a given cytokine in vivo. Instead, individual RE differentially contribute to proper genomic positioning of REs and target genes. RE deletions resulted in context-dependent dysregulation of cytokine expression and immune response in tissue. Thus, signal-dependent remodeling of three-dimensional configuration underlies divergent cytokine outputs from the type 2 loci.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"1 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673220","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

Author Correction: NK cell receptor NKG2D sets activation threshold for the NCR1 receptor early in NK cell development 作者更正：NK细胞受体NKG2D在NK细胞发育早期为NCR1受体设定激活阈值

IF 30.5 1区医学

Nature Immunology Pub Date : 2024-11-19 DOI: 10.1038/s41590-024-02038-x

Vedrana Jelenčić, Marko Šestan, Inga Kavazović, Maja Lenartić, Sonja Marinović, Tim D. Holmes, Michaela Prchal-Murphy, Berislav Lisnić, Veronika Sexl, Yenan T. Bryceson, Felix M. Wensveen, Bojan Polić

引用次数: 0

B cells infiltrate cutaneous T cell lymphomas B 细胞浸润皮肤 T 细胞淋巴瘤

IF 30.5 1区医学

Nature Immunology Pub Date : 2024-11-19 DOI: 10.1038/s41590-024-02022-5

引用次数: 0

Cutaneous T cell lymphoma atlas reveals malignant TH2 cells supported by a B cell-rich tumor microenvironment 皮肤 T 细胞淋巴瘤图谱揭示了由富含 B 细胞的肿瘤微环境支持的恶性 TH2 细胞

IF 30.5 1区医学

Nature Immunology Pub Date : 2024-11-18 DOI: 10.1038/s41590-024-02018-1

Ruoyan Li, Johanna Strobl, Elizabeth F. M. Poyner, Aya Balbaa, Fereshteh Torabi, Pavel V. Mazin, Nana-Jane Chipampe, Emily Stephenson, Ciro Ramírez-Suástegi, Vijaya Baskar Mahalingam Shanmugiah, Louis Gardner, Bayanne Olabi, Rowen Coulthard, Rachel A. Botting, Nina Zila, Elena Prigmore, Nusayhah H. Gopee, Marta A. Chroscik, Efpraxia Kritikaki, Justin Engelbert, Issac Goh, Hon Man Chan, Harriet F. Johnson, Jasmine Ellis, Victoria Rowe, Win Tun, Gary Reynolds, Dexin Yang, April Rose Foster, Laure Gambardella, Elena Winheim, Chloe Admane, Benjamin Rumney, Lloyd Steele, Laura Jardine, Julia Nenonen, Keir Pickard, Jennifer Lumley, Philip Hampton, Simeng Hu, Fengjie Liu, Xiangjun Liu, David Horsfall, Daniela Basurto-Lozada, Louise Grimble, Chris M. Bacon, Sophie C. Weatherhead, Hanna Brauner, Yang Wang, Fan Bai, Nick J. Reynolds, Judith E. Allen, Constanze Jonak, Patrick M. Brunner, Sarah A. Teichmann, Muzlifah Haniffa

{"title":"Cutaneous T cell lymphoma atlas reveals malignant TH2 cells supported by a B cell-rich tumor microenvironment","authors":"Ruoyan Li, Johanna Strobl, Elizabeth F. M. Poyner, Aya Balbaa, Fereshteh Torabi, Pavel V. Mazin, Nana-Jane Chipampe, Emily Stephenson, Ciro Ramírez-Suástegi, Vijaya Baskar Mahalingam Shanmugiah, Louis Gardner, Bayanne Olabi, Rowen Coulthard, Rachel A. Botting, Nina Zila, Elena Prigmore, Nusayhah H. Gopee, Marta A. Chroscik, Efpraxia Kritikaki, Justin Engelbert, Issac Goh, Hon Man Chan, Harriet F. Johnson, Jasmine Ellis, Victoria Rowe, Win Tun, Gary Reynolds, Dexin Yang, April Rose Foster, Laure Gambardella, Elena Winheim, Chloe Admane, Benjamin Rumney, Lloyd Steele, Laura Jardine, Julia Nenonen, Keir Pickard, Jennifer Lumley, Philip Hampton, Simeng Hu, Fengjie Liu, Xiangjun Liu, David Horsfall, Daniela Basurto-Lozada, Louise Grimble, Chris M. Bacon, Sophie C. Weatherhead, Hanna Brauner, Yang Wang, Fan Bai, Nick J. Reynolds, Judith E. Allen, Constanze Jonak, Patrick M. Brunner, Sarah A. Teichmann, Muzlifah Haniffa","doi":"10.1038/s41590-024-02018-1","DOIUrl":"https://doi.org/10.1038/s41590-024-02018-1","url":null,"abstract":"Cutaneous T cell lymphoma (CTCL) is a potentially fatal clonal malignancy of T cells primarily affecting the skin. The most common form of CTCL, mycosis fungoides, can be difficult to diagnose, resulting in treatment delay. We performed single-cell and spatial transcriptomics analysis of skin from patients with mycosis fungoides-type CTCL and an integrated comparative analysis with human skin cell atlas datasets from healthy and inflamed skin. We revealed the co-optation of T helper 2 (TH2) cell-immune gene programs by malignant CTCL cells and modeling of the tumor microenvironment to support their survival. We identified MHC-II+ fibroblasts and dendritic cells that can maintain TH2 cell-like tumor cells. CTCL tumor cells are spatially associated with B cells, forming tertiary lymphoid structure-like aggregates. Finally, we validated the enrichment of B cells in CTCL and its association with disease progression across three independent patient cohorts. Our findings provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for CTCL.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"249 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665528","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

Disease-associated B cells and immune endotypes shape adaptive immune responses to SARS-CoV-2 mRNA vaccination in human SLE 疾病相关 B 细胞和免疫内型决定了人类系统性红斑狼疮患者对 SARS-CoV-2 mRNA 疫苗接种的适应性免疫反应

IF 30.5 1区医学

Nature Immunology Pub Date : 2024-11-12 DOI: 10.1038/s41590-024-02010-9

Caterina E. Faliti, Trinh T. P. Van, Fabliha A. Anam, Narayanaiah Cheedarla, M. Elliott Williams, Ashish Kumar Mishra, Sabeena Y. Usman, Matthew C. Woodruff, Geoff Kraker, Martin C. Runnstrom, Shuya Kyu, Daniel Sanz, Hasan Ahmed, Midushi Ghimire, Andrea Morrison-Porter, Hannah Quehl, Natalie S. Haddad, Weirong Chen, Suneethamma Cheedarla, Andrew S. Neish, John D. Roback, Rustom Antia, Jennifer Hom, Christopher M. Tipton, John M. Lindner, Eliver Ghosn, Surender Khurana, Christopher D. Scharer, Arezou Khosroshahi, F. Eun-Hyung Lee, Ignacio Sanz

{"title":"Disease-associated B cells and immune endotypes shape adaptive immune responses to SARS-CoV-2 mRNA vaccination in human SLE","authors":"Caterina E. Faliti, Trinh T. P. Van, Fabliha A. Anam, Narayanaiah Cheedarla, M. Elliott Williams, Ashish Kumar Mishra, Sabeena Y. Usman, Matthew C. Woodruff, Geoff Kraker, Martin C. Runnstrom, Shuya Kyu, Daniel Sanz, Hasan Ahmed, Midushi Ghimire, Andrea Morrison-Porter, Hannah Quehl, Natalie S. Haddad, Weirong Chen, Suneethamma Cheedarla, Andrew S. Neish, John D. Roback, Rustom Antia, Jennifer Hom, Christopher M. Tipton, John M. Lindner, Eliver Ghosn, Surender Khurana, Christopher D. Scharer, Arezou Khosroshahi, F. Eun-Hyung Lee, Ignacio Sanz","doi":"10.1038/s41590-024-02010-9","DOIUrl":"https://doi.org/10.1038/s41590-024-02010-9","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 mRNA vaccination has reduced effectiveness in certain immunocompromised individuals. However, the cellular mechanisms underlying these defects, as well as the contribution of disease-induced cellular abnormalities, remain largely unexplored. In this study, we conducted a comprehensive serological and cellular analysis of patients with autoimmune systemic lupus erythematosus (SLE) who received the Wuhan-Hu-1 monovalent mRNA coronavirus disease 2019 vaccine. Our findings revealed that patients with SLE exhibited reduced avidity of anti-receptor-binding domain antibodies, leading to decreased neutralization potency and breadth. We also observed a sustained anti-spike response in IgD−CD27− ‘double-negative (DN)’ DN2/DN3 B cell populations persisting during memory responses and with greater representation in the SLE cohort. Additionally, patients with SLE displayed compromised anti-spike T cell immunity. Notably, low vaccine efficacy strongly correlated with higher values of a newly developed extrafollicular B and T cell score, supporting the importance of distinct B cell endotypes. Finally, we found that anti-BAFF blockade through belimumab treatment was associated with poor vaccine immunogenicity due to inhibition of naive B cell priming and an unexpected impact on circulating T follicular helper cells.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"71 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599626","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

Immune drivers of pain resolution and protection 缓解和保护疼痛的免疫驱动因素

IF 30.5 1区医学

Nature Immunology Pub Date : 2024-11-11 DOI: 10.1038/s41590-024-02002-9

Sara Hakim, Aakanksha Jain, Clifford J. Woolf

引用次数: 0