Science Immunology最新文献_第9页

Erratum for the Research Article “The chemerin-CMKLR1 axis limits thermogenesis by controlling a beige adipocyte/IL-33/type 2 innate immunity circuit” 研究文章“chemerin-CMKLR1轴通过控制米色脂肪细胞/IL-33/ 2型先天免疫回路限制产热”的更正。

IF 16.3 1区医学

Science Immunology Pub Date : 2026-04-24 DOI: 10.1126/sciimmunol.aeh5833

引用次数: 0

An adaptive cellular source of IL-17A and IL-17F is critical for the induction of experimental autoimmune encephalomyelitis IL-17A和IL-17F的适应性细胞来源对实验性自身免疫性脑脊髓炎的诱导至关重要

IF 16.3 1区医学

Science Immunology Pub Date : 2026-04-24 DOI: 10.1126/sciimmunol.aee1481

Allen W. Ho, Linglin Huang, Sumiti Sandhu, Sheng Xiao, Melissa Sgodzai, Ella Ullerich, Rajesh K. Krishnan, Alexandra Schnell, Vijay K. Kuchroo

{"title":"An adaptive cellular source of IL-17A and IL-17F is critical for the induction of experimental autoimmune encephalomyelitis","authors":"Allen W. Ho, Linglin Huang, Sumiti Sandhu, Sheng Xiao, Melissa Sgodzai, Ella Ullerich, Rajesh K. Krishnan, Alexandra Schnell, Vijay K. Kuchroo","doi":"10.1126/sciimmunol.aee1481","DOIUrl":"10.1126/sciimmunol.aee1481","url":null,"abstract":"<div >T helper 17 (T<sub>H</sub>17) cells are thought to play an important role in the pathogenesis of many autoimmune disorders, including multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). However, recent studies have suggested that interleukin-17 (IL-17) may be dispensable for the induction of EAE. Here, we use an adoptive transfer model of EAE to demonstrate that an adaptive cellular source of IL-17 is absolutely required for the induction of EAE disease. We further show that B cells can regulate the transfer of EAE disease in this context. Transcriptional profiling of T<sub>H</sub>17 cells in our model suggests that loss of IL-17A/F in T cells results in a lack of an IL-23 receptor (IL-23R)–driven signaling signature. Our data demonstrate the critical importance of an adaptive immune cellular source of IL-17A and IL-17F to mediate EAE and that IL-17 signaling is required for IL-23–mediated T<sub>H</sub>17 cell pathogenicity.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 118","pages":""},"PeriodicalIF":16.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147736782","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 autoantigen TRIM21 assembles proinflammatory immune complexes after lytic cell death 自身抗原TRIM21在溶解细胞死亡后组装促炎免疫复合物

IF 16.3 1区医学

Science Immunology Pub Date : 2026-04-17 DOI: 10.1126/sciimmunol.ads9680

Esther L. Jones Evans, Benjamin Demarco, Han Cai, Madelon M.E. de Jong, Sarah Hill, Marcus A. Widdess, Joannah R. Fergusson, Ryan E. Glass, Gemma Harris, Gracie J. Mead, Yavuz F. Yazicioglu, Saba Nayar, Benjamin A. Fisher, Mark S. Cragg, Alexander J. Clarke, Audrey Gérard, Jelena S. Bezbradica, Lynn B. Dustin

{"title":"The autoantigen TRIM21 assembles proinflammatory immune complexes after lytic cell death","authors":"Esther L. Jones Evans, Benjamin Demarco, Han Cai, Madelon M.E. de Jong, Sarah Hill, Marcus A. Widdess, Joannah R. Fergusson, Ryan E. Glass, Gemma Harris, Gracie J. Mead, Yavuz F. Yazicioglu, Saba Nayar, Benjamin A. Fisher, Mark S. Cragg, Alexander J. Clarke, Audrey Gérard, Jelena S. Bezbradica, Lynn B. Dustin","doi":"10.1126/sciimmunol.ads9680","DOIUrl":"10.1126/sciimmunol.ads9680","url":null,"abstract":"<div >Sjögren’s disease (SjD) causes localized and systemic inflammation and autoantibody production against intracellular proteins such as TRIM21/Ro52 (tripartite motif-containing protein 21). TRIM21, an E3 ubiquitin ligase, binds antibody Fc domains on opsonized pathogens that have escaped extracellular immunity and entered the cytosol. TRIM21 then ubiquitinates these pathogens, driving their proteasomal degradation. How TRIM21 becomes an autoantigen remains unclear. We show that TRIM21 is released upon lytic cell death (pyroptosis or necroptosis) but not apoptosis. Although many cytosolic proteins are released by dead cells, liberated TRIM21 is distinct: Its high antibody affinity enables binding to Fc domains of circulating immunoglobulins, forming large immune complexes (ICs). These ICs increase in SjD, where anti-TRIM21 autoantibodies interact with released TRIM21 via Fc and F(ab′)<sub>2</sub>. TRIM21 ICs are taken up by macrophages, which drive proinflammatory responses, antigen presentation, and metabolic changes in high interferon environments. Thus, TRIM21 may perpetuate inflammation and autoantigen presentation, resulting in high immunogenicity.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 118","pages":""},"PeriodicalIF":16.3,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147695559","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

Gene delivery of immunomodulatory cytokines to the lung preserves respiratory function during inflammatory challenge 免疫调节细胞因子的基因传递到肺在炎症挑战期间保持呼吸功能

IF 16.3 1区医学

Science Immunology Pub Date : 2026-04-17 DOI: 10.1126/sciimmunol.adv7969

Ntombizodwa Makuyana, Laura Seldeslachts, Lauren Michiels, Oliver T. Burton, Alvaro R. Hernandez, Arman Ghodsinia, Ekhlas Rahman, Laura M. Kops, Kailash Singh, Fran Naranjo, Magda Ali, Amy Dashwood, Marwane Achkir, Lubna Kouser, Stephanie Lienart, Stephane Guillaume, Lieve Naesens, Michelle A. Linterman, Joost Wauters, Régis Joulia, Stephanie Humblet-Baron, Greetje Vande Velde, James Dooley, Adrian Liston

{"title":"Gene delivery of immunomodulatory cytokines to the lung preserves respiratory function during inflammatory challenge","authors":"Ntombizodwa Makuyana, Laura Seldeslachts, Lauren Michiels, Oliver T. Burton, Alvaro R. Hernandez, Arman Ghodsinia, Ekhlas Rahman, Laura M. Kops, Kailash Singh, Fran Naranjo, Magda Ali, Amy Dashwood, Marwane Achkir, Lubna Kouser, Stephanie Lienart, Stephane Guillaume, Lieve Naesens, Michelle A. Linterman, Joost Wauters, Régis Joulia, Stephanie Humblet-Baron, Greetje Vande Velde, James Dooley, Adrian Liston","doi":"10.1126/sciimmunol.adv7969","DOIUrl":"10.1126/sciimmunol.adv7969","url":null,"abstract":"<div >Respiratory infections that result in severe and life-threatening immune-mediated respiratory decline are a major public health issue. Controlling local respiratory immune reactions without the use of systemic immunosuppressants remains an unmet clinical challenge. We developed a gene delivery system to express anti-inflammatory cytokines in the lung, which reestablishes local immune homeostasis without triggering systemic effects. Using an adeno-associated vector cargo system (AAV6.2-<i>CC10</i>), we induced production of interleukin-2 (IL-2), IL-1 receptor antagonist (IL-1RA), and IL-10 in situ in the lung microenvironment, with no detectable expression or immunological deviation in the peripheral immune system. We demonstrate the effective potential of IL-2, IL-1RA, and IL-10 as immunomodulatory cargos in severe infectious challenge, which reduced respiratory pathology after influenza-associated pulmonary aspergillosis. Thus, the AAV6.2-<i>CC10</i> platform enables targeted delivery of biologics to the lung, modulates the lung environment, and improves pathology without inducing systemic immune reactions.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 118","pages":""},"PeriodicalIF":16.3,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147695557","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

Divergent granulopoiesis at extramedullary sites safeguards antibacterial host defense 在髓外部位分散的颗粒形成保护抗菌宿主防御

IF 16.3 1区医学

Science Immunology Pub Date : 2026-04-17 DOI: 10.1126/sciimmunol.adw7077

Carlos Silvestre-Roig, Raphael Chevre, Merieme Farjia, Alexander Bender, Lina M. Vöcking, Mathis Richter, Ali Hageb, Vincent Suerdieck, Francisco J. Arenas Cerro, Quinte Braster, Mauricio Guzman, Jordi Sintes, Samriti Sharma, Patricia Lemnitzer, Claudia Tulotta, Yvonne Börgeling, Andrea Herrero-Cervera, Hannah Flueter, Sara Noemi Reinartz Groba, David Ahern, Collins Osei-Sarpong, Ralf Zimmer, Noelia Alonso-Gonzalez, Eduardo Ortega, Stefan Lienenklaus, Ulrich Kalinke, Stephan Ludwig, Daniel R. Engel, Frank Rosenbauer, Claudia Monaco, Petra Dersch, Artur Kibler, Andrea Cerutti, Triantafyllos Chavakis, Rui Benedito, Andres Hidalgo, Jadwiga Jablonska, Miguel Palomino-Segura, Oliver Soehnlein

{"title":"Divergent granulopoiesis at extramedullary sites safeguards antibacterial host defense","authors":"Carlos Silvestre-Roig, Raphael Chevre, Merieme Farjia, Alexander Bender, Lina M. Vöcking, Mathis Richter, Ali Hageb, Vincent Suerdieck, Francisco J. Arenas Cerro, Quinte Braster, Mauricio Guzman, Jordi Sintes, Samriti Sharma, Patricia Lemnitzer, Claudia Tulotta, Yvonne Börgeling, Andrea Herrero-Cervera, Hannah Flueter, Sara Noemi Reinartz Groba, David Ahern, Collins Osei-Sarpong, Ralf Zimmer, Noelia Alonso-Gonzalez, Eduardo Ortega, Stefan Lienenklaus, Ulrich Kalinke, Stephan Ludwig, Daniel R. Engel, Frank Rosenbauer, Claudia Monaco, Petra Dersch, Artur Kibler, Andrea Cerutti, Triantafyllos Chavakis, Rui Benedito, Andres Hidalgo, Jadwiga Jablonska, Miguel Palomino-Segura, Oliver Soehnlein","doi":"10.1126/sciimmunol.adw7077","DOIUrl":"10.1126/sciimmunol.adw7077","url":null,"abstract":"<div >Extramedullary organs such as the spleen can assume granulopoiesis as a supportive mechanism to cope with increased demands during persistent inflammation. However, the quantitative output of extramedullary granulopoiesis is limited, and whether the spleen provides neutrophils of a qualitative difference remains unclear. Here, we found that splenic stress granulopoiesis is associated with distinct neutrophil production and differentiation trajectories. Myeloid progenitors in the spleen engaged in accelerated production of neutrophils with an immature phenotype. Yet, neutrophils generated during persistent stress granulopoiesis were fully competent to exert antimicrobial functions and were necessary to contain bacterial invasion in the bladder. Activation of type I interferon signaling in the spleen was required for splenic neutrophil priming, and its loss impaired antibacterial host defense. Thus, the spleen provides an immunological environment for stress-induced rapid production and priming of highly active neutrophils to meet demands during infection.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 118","pages":""},"PeriodicalIF":16.3,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147695675","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

Single-cell TCR mapping reveals spatially coordinated T cell states in head and neck cancer 单细胞TCR图谱揭示头颈癌中空间协调的T细胞状态

IF 16.3 1区医学

Science Immunology Pub Date : 2026-04-10 DOI: 10.1126/sciimmunol.aec3133

Kelli A. McCord, Emerald Kan, Sean Hyslop, Amanda Y. Xia, Colby J. Hofferek, James S. Lewis Jr., Andreas Wieland, David J. Hernandez, Vlad C. Sandulache, William H. Hudson

{"title":"Single-cell TCR mapping reveals spatially coordinated T cell states in head and neck cancer","authors":"Kelli A. McCord, Emerald Kan, Sean Hyslop, Amanda Y. Xia, Colby J. Hofferek, James S. Lewis Jr., Andreas Wieland, David J. Hernandez, Vlad C. Sandulache, William H. Hudson","doi":"10.1126/sciimmunol.aec3133","DOIUrl":"10.1126/sciimmunol.aec3133","url":null,"abstract":"<div >Current spatial T cell receptor (TCR) profiling approaches lack the resolution needed to link clonal identity, transcriptional state, and spatial positioning of individual T cells in the tumor microenvironment. Here, we introduce a spatial TCR profiling strategy that resolves individual T cell clones together with their transcriptional states at single-cell resolution and applied the method to human head and neck squamous cell carcinoma. Presumed tumor-specific T cells were broadly dispersed throughout the tumor microenvironment, and cells of the same clone occupied distinct transcriptional states in different locations: Immune-rich regions contained more plastic or progenitor cells, whereas tumor-dense regions were enriched for exhausted states. Patients exhibited notably different spatial architectures of antitumor T cell responses, revealing variation that was not captured by high-resolution, spatially agnostic methods such as spectral flow cytometry and single-cell RNA sequencing. These results provide a blueprint for dissecting antigen-specific T cell states in human tumors and reveal how T cell states are spatially coordinated with local cues across the tumor microenvironment.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 118","pages":""},"PeriodicalIF":16.3,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643270","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

Intratumoral Treg cell ablation elicits NK cell–mediated control of CD8 T cell–resistant tumors 肿瘤内Treg细胞消融引发NK细胞介导的CD8 T细胞耐药肿瘤的控制

IF 16.3 1区医学

Science Immunology Pub Date : 2026-04-10 DOI: 10.1126/sciimmunol.adx4411

Chenyu Zhang, Charles Chien, Eglė Jurgaitytė, Koharu Sakiyama, Alissa Bockman, Yeara Jo, Seungwon Lee, Stephanie Silveria, Elizabeth Andrews, Abigail Mende, Lily Zhang, K. Christopher Garcia, Allon Wagner, Michel DuPage, David Raulet

{"title":"Intratumoral Treg cell ablation elicits NK cell–mediated control of CD8 T cell–resistant tumors","authors":"Chenyu Zhang, Charles Chien, Eglė Jurgaitytė, Koharu Sakiyama, Alissa Bockman, Yeara Jo, Seungwon Lee, Stephanie Silveria, Elizabeth Andrews, Abigail Mende, Lily Zhang, K. Christopher Garcia, Allon Wagner, Michel DuPage, David Raulet","doi":"10.1126/sciimmunol.adx4411","DOIUrl":"10.1126/sciimmunol.adx4411","url":null,"abstract":"<div >Cancer cells frequently lose major histocompatibility complex class I (MHC I) to evade CD8 T cell recognition. Natural killer (NK) cells are poised to target MHC I–deficient cancer cells, but MHC I loss alone is often insufficient to unleash fully effective NK cell responses. Here, we show that selective intratumoral (IT) ablation of regulatory T cells (T<sub>reg</sub> cells) elicited potent antitumor NK cell responses that controlled MHC I–deficient and even MHC I<sup>+</sup> cancers that expressed NKG2D ligands. T<sub>reg</sub> cells controlled the activation, maturation, and antitumor cytotoxic activity of NK cells within the tumor microenvironment. Mechanistically, depletion of IT-T<sub>reg</sub> cells relieved the inhibition of cDC2-dependent induction of IL-2 production by conventional CD4 T cells that was necessary for NK cell activation. Systemically administered antibodies that selectively depleted IT-T<sub>reg</sub> cells similarly empowered NK cell–dependent tumor control. These findings expand the breadth of T<sub>reg</sub> cell–mediated cancer immunosuppression to encompass antitumor NK cells and suggest that therapeutic targeting of T<sub>reg</sub> cells in tumors can control CD8 T cell–resistant cancers.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 118","pages":""},"PeriodicalIF":16.3,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643269","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

Erratum for the Research Article “A noncanonical cytoplasmic role for BUB1 in restraining DNA damage–induced dsRNA accumulation and sensing within stress granules” 研究文章“BUB1在抑制DNA损伤诱导的dsRNA积累和感知中的非规范细胞质作用”的勘误

IF 16.3 1区医学

Science Immunology Pub Date : 2026-04-10 DOI: 10.1126/sciimmunol.aeh4448

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The rise of spatial TCR profiling: Emerging technologies and open challenges 空间TCR分析的兴起：新兴技术和开放挑战

IF 16.3 1区医学

Science Immunology Pub Date : 2026-04-10 DOI: 10.1126/sciimmunol.aeg7517

Yinglu Tang, Tao Wang

引用次数: 0

The epitope tax: Antibody feedback and the economics of germinal center competition 表位税：抗体反馈与生发中心竞争的经济学

IF 16.3 1区医学