Science Immunology最新文献_第7页

IF 16.3 1区医学

Science Immunology Pub Date : 2026-06-05 DOI: 10.1126/sciimmunol.aej1954

Jada M. Coffey, Gabriel K. Griffin

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Cytotoxic CD39+ tumor-associated NK cells respond to NKG2A blockade in lung cancer 肺癌中细胞毒性CD39+肿瘤相关NK细胞对NKG2A阻断有反应

IF 16.3 1区医学

Science Immunology Pub Date : 2026-06-05 DOI: 10.1126/sciimmunol.aeb6645

Clara Serger, Lucas Rebuffet, Michael T. Sandholzer, Wiebke Rackwitz, Irene Fusi, Petra Herzig, Annalea Brüggemann, Carina A. Pawlow, Evgeny Chichelnitskiy, Daniel Hajnal, Nicole Oelgarth, Sarp Uzun, Christoph Schultheiß, Andreas Zingg, Sofia Tundo, Thuy T. Luu, Aljaz Hojski, Didier Lardinois, Lavinia Neubert, Mascha Binder, Kirsten Mertz, Marcel P. Trefny, Nicole Kirchhammer, Marina Natoli, Matthias S. Matter, Heinz Läubli, Christine Falk, Karin Schaeuble, Eric Vivier, Andrea Romagnani, Alfred Zippelius

{"title":"Cytotoxic CD39+ tumor-associated NK cells respond to NKG2A blockade in lung cancer","authors":"Clara Serger, Lucas Rebuffet, Michael T. Sandholzer, Wiebke Rackwitz, Irene Fusi, Petra Herzig, Annalea Brüggemann, Carina A. Pawlow, Evgeny Chichelnitskiy, Daniel Hajnal, Nicole Oelgarth, Sarp Uzun, Christoph Schultheiß, Andreas Zingg, Sofia Tundo, Thuy T. Luu, Aljaz Hojski, Didier Lardinois, Lavinia Neubert, Mascha Binder, Kirsten Mertz, Marcel P. Trefny, Nicole Kirchhammer, Marina Natoli, Matthias S. Matter, Heinz Läubli, Christine Falk, Karin Schaeuble, Eric Vivier, Andrea Romagnani, Alfred Zippelius","doi":"10.1126/sciimmunol.aeb6645","DOIUrl":"10.1126/sciimmunol.aeb6645","url":null,"abstract":"<div >Natural killer (NK) cell–targeting immunotherapies are emerging, yet the differentiation and functional states of tumor-infiltrating NK cells remain poorly understood. Using matched single-nucleus RNA and ATAC sequencing of samples from patients with non–small cell lung cancer (NSCLC), we resolved the transcriptional and epigenetic landscape of intratumoral NK cells. We identified two tumor-associated NK (taNK) cell subsets marked by expression of <i>ITGAE</i> (CD103) and <i>ITGA1</i> (CD49a) that display features of tissue residency and dysfunction while preserving cytotoxic function. Trajectory and regulon analyses revealed an inflammation-driven transition from early <i>granzyme K</i> (<i>GZMK</i>)<sup>+</sup> NK cells toward an <i>ENTPD1</i><sup>+</sup> (CD39<sup>+</sup>) effector state characterized by interferon-stimulated gene (ISG) programs. Functional profiling established CD39<sup>+</sup> taNK cells as the dominant cytotoxic NK cell population with superior killing capacity that was further potentiated by NKG2A blockade. This study offers mechanistic insights into NK cell differentiation in NSCLC and establishes CD39<sup>+</sup> taNK cells as a targetable effector population for immunotherapy.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 120","pages":""},"PeriodicalIF":16.3,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.aeb6645","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148167232","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}

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Atlas of human gut-associated lymphoid tissue reveals immunomodulatory interactions of B cells 人类肠道相关淋巴组织图谱揭示了B细胞的免疫调节相互作用

IF 16.3 1区医学

Science Immunology Pub Date : 2026-06-05 DOI: 10.1126/sciimmunol.ady8948

Michael J. Pitcher, Xiaowen Sun, Chiara Dionisi, Lucia Montorsi, Sherine H. Kottoor, Jacqueline H. Y. Siu, Roman Laddach, Rosamond Nuamah, Gavin J. Pettigrew, Richard J. Ellis, Cynthia Bishop, Jahangir Sufi, Pawan Dhami, Heli Vaikkinen, Audrey Kelly, Anna Vossenkamper, Deena L. Gibbons, Jo Spencer

{"title":"Atlas of human gut-associated lymphoid tissue reveals immunomodulatory interactions of B cells","authors":"Michael J. Pitcher, Xiaowen Sun, Chiara Dionisi, Lucia Montorsi, Sherine H. Kottoor, Jacqueline H. Y. Siu, Roman Laddach, Rosamond Nuamah, Gavin J. Pettigrew, Richard J. Ellis, Cynthia Bishop, Jahangir Sufi, Pawan Dhami, Heli Vaikkinen, Audrey Kelly, Anna Vossenkamper, Deena L. Gibbons, Jo Spencer","doi":"10.1126/sciimmunol.ady8948","DOIUrl":"10.1126/sciimmunol.ady8948","url":null,"abstract":"<div >Gut-associated lymphoid tissue (GALT) is organized lymphoid tissue that responds chronically to antigens, including whole bacteria, sampled from the gut lumen. The ensuing immunoglobulin A (IgA) plasma cell response disseminates to regulate bacterial populations and to mediate intestinal immune homeostasis. GALT has roles in the development of the innate-like marginal zone B cell population and is associated with a B cell–mediated contribution to ulcerative colitis (UC) severity and response to therapy. Applying integrated multiomics methodologies, we identified key spatially resolved interactions of B cell subsets including broad regulatory features of double negative 2 (DN2) B cells with potential to maintain homeostasis within microbe-rich mucosa. By contrast, GALT in UC is distorted in composition and spatial distribution of B cell subsets that have altered immunomodulatory potential compared with healthy GALT. Thus, we identify interactions of strategically located B cells as mediators of immunological equilibrium in human gut.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 120","pages":""},"PeriodicalIF":16.3,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.ady8948","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148167230","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}

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Transcriptional and chromatin dynamics in macrophage differentiation and activation 巨噬细胞分化和激活中的转录和染色质动力学。

IF 16.3 1区医学

Science Immunology Pub Date : 2026-05-29 DOI: 10.1126/sciimmunol.aec1740

Marten A. Hoeksema, Annette E. Neele, Koen H. M. Prange, Christopher K. Glass, Menno P. J. de Winther

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Mitochondrial complex I activity promotes antigen cross-presentation in dendritic cells 线粒体复合体I的活性促进抗原在树突状细胞中的交叉递呈。

IF 16.3 1区医学

Science Immunology Pub Date : 2026-05-22 DOI: 10.1126/sciimmunol.aef0098

Sofía C. Khouili, Elena Priego, Ignacio Heras-Murillo, Gillian Dunphy, Annalaura Mastrangelo, Sarai Martínez-Cano, Vanessa Nuñez, Manuel Rodrigo-Tapias, Adrián Belinchón-García, Johan Garaude, Salvador Iborra, Navdeep S. Chandel, Patricia González-Rodríguez, Michel Enamorado, David Sancho

{"title":"Mitochondrial complex I activity promotes antigen cross-presentation in dendritic cells","authors":"Sofía C. Khouili, Elena Priego, Ignacio Heras-Murillo, Gillian Dunphy, Annalaura Mastrangelo, Sarai Martínez-Cano, Vanessa Nuñez, Manuel Rodrigo-Tapias, Adrián Belinchón-García, Johan Garaude, Salvador Iborra, Navdeep S. Chandel, Patricia González-Rodríguez, Michel Enamorado, David Sancho","doi":"10.1126/sciimmunol.aef0098","DOIUrl":"10.1126/sciimmunol.aef0098","url":null,"abstract":"<div >Mitochondrial metabolism modulates immune cell signaling, yet how individual electron transport chain complexes fine-tune dendritic cell (DC) function remains unclear. Here, we identify mitochondrial complex I (CI) as a critical metabolic checkpoint controlling antigen cross-presentation by DCs in mice. Deficiency of the CI subunit NDUFS4 in DCs led to the formation of a nonfunctional CI subcomplex, resulting in mildly impaired mitochondrial respiration without triggering a compensatory glycolytic shift. NDUFS4 deficiency limited endosomal escape of internalized antigens, thereby impairing antigen cross-presentation while largely preserving direct presentation. CI dysfunction lowered the NAD<sup>+</sup>/NADH ratio, concomitant with decreased ATP levels, and diminished neutral lipid storage and lipid peroxidation. Restoration of the NAD<sup>+</sup>/NADH ratio rescued cross-presentation in NDUFS4-deficient DCs. NDUFS2-deficient DCs showed similar defects in cross-presentation, which were also rescued by rebalancing the NAD<sup>+</sup>/NADH ratio. Together, these findings reveal a link between mitochondrial CI integrity, NAD<sup>+</sup>-driven redox metabolism, and antigen cross-presentation.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 119","pages":""},"PeriodicalIF":16.3,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148006584","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}

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Gastrointestinal tuft cells: Recent insights and next questions 胃肠道簇状细胞：最近的见解和下一个问题。

IF 16.3 1区医学

Science Immunology Pub Date : 2026-05-22 DOI: 10.1126/sciimmunol.aea8740

Thornton W. Thompson, Jakob von Moltke

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PD-1 signaling and PD-1 blockade–mediated tumor control are established at microvillar T cell contacts PD-1信号和PD-1阻断介导的肿瘤控制是在微绒毛T细胞接触中建立的

IF 16.3 1区医学

Science Immunology Pub Date : 2026-05-15 DOI: 10.1126/sciimmunol.adz4983

Edward Jenkins, Martin Fellermeyer, Daniel F. Heraghty, Sumana Sharma, Tanmay Mitra, Mateusz Kotowski, Joseph Clarke, Yuan Lui, Sam Daly, Zach Marin, Debasis Banik, Markus Körbel, Emily Zhi Qing Ng, Thomas Lister, Ana Mafalda Santos, Steven F. Lee, Michael L. Dustin, Simon J. Davis, David Klenerman

{"title":"PD-1 signaling and PD-1 blockade–mediated tumor control are established at microvillar T cell contacts","authors":"Edward Jenkins, Martin Fellermeyer, Daniel F. Heraghty, Sumana Sharma, Tanmay Mitra, Mateusz Kotowski, Joseph Clarke, Yuan Lui, Sam Daly, Zach Marin, Debasis Banik, Markus Körbel, Emily Zhi Qing Ng, Thomas Lister, Ana Mafalda Santos, Steven F. Lee, Michael L. Dustin, Simon J. Davis, David Klenerman","doi":"10.1126/sciimmunol.adz4983","DOIUrl":"10.1126/sciimmunol.adz4983","url":null,"abstract":"<div >Lymphocyte activation relies on the integration of signals from multiple receptors at cell-cell contacts, but the spatiotemporal regulation of this process is unclear. Here, we show that programmed cell death protein 1 (PD-1) and T cell receptor (TCR) signals are integrated at nanoscale microvillar close contacts formed during T cell interactions with their targets. PD-1 signaling begins as these contacts form and selectively limits the duration, but not the amplitude, of TCR signaling. PD-1 suppresses TCR activity directly, by locally recruiting Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP2), and indirectly, by reducing cell-spreading, close-contact formation, and TCR engagement. A PD-1 blocking antibody induced inhibitory signaling when Fc receptor engagement trapped PD-1 at close contacts. Engineering the antibody to prevent PD-1 trapping eliminated these agonistic effects and improved blockade efficacy. These findings identify microvillar contacts as crucial hubs of initial signal integration and provide a framework for optimizing checkpoint immunotherapies.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 119","pages":""},"PeriodicalIF":16.3,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147938878","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}

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Goblet cells tune ILC2 activity through a gut-specific response checkpoint 杯状细胞通过肠道特异性反应检查点调节ILC2活性

IF 16.3 1区医学

Science Immunology Pub Date : 2026-05-15 DOI: 10.1126/sciimmunol.adu1870

Kyle Burrows, Louis Ngai, Siu Ling Tai, Pailin Chiaranunt, Edward L. Y. Chen, Manjula Kamath, Juan Carlos Zúñiga-Pflücker, Arthur Mortha

{"title":"Goblet cells tune ILC2 activity through a gut-specific response checkpoint","authors":"Kyle Burrows, Louis Ngai, Siu Ling Tai, Pailin Chiaranunt, Edward L. Y. Chen, Manjula Kamath, Juan Carlos Zúñiga-Pflücker, Arthur Mortha","doi":"10.1126/sciimmunol.adu1870","DOIUrl":"10.1126/sciimmunol.adu1870","url":null,"abstract":"<div >Group 2 innate lymphoid cells (ILC2s) support tissue homeostasis and type 2 inflammation. ILC2s, which are found in many tissues, adapt to local cues to perform tissue-specific functions. Intestinal ILC2s rapidly respond to helminth and protozoan infections via cross-talk with tuft cells, but the mechanism guiding this adaptation remains unclear. Here, we identify Notch signaling, triggered by the ligand Delta-like 1 on goblet cells, as a key regulator of gut ILC2 specialization in mice. Loss of the Notch signaling protein RBPJ did not impair ILC2 development but altered the expression of interleukin-33 (IL-33) and IL-25 receptors (ST2 and IL-17RB, respectively) on gut ILC2s. This increased sensitivity to IL-33, promoted IL-5 and IL-13 production, and drove the expansion of gut eosinophils and goblet cells. Moreover, RBPJ-deficient ILC2s failed to respond to tuft cell–derived IL-25 after <i>Tritrichomonas musculis</i> colonization. Thus, RBPJ-dependent Notch responsiveness in ILC2s regulates intestinal tissue adaptation and primes the tuft cell–ILC2 circuit for intestinal homeostasis.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 119","pages":""},"PeriodicalIF":16.3,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147938877","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}

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Erratum for the Research Article “Single-cell profiling reveals diverse γδ T cell subsets in ulcerative colitis” 研究文章“单细胞谱揭示溃疡性结肠炎中不同的γδ T细胞亚群”的勘误

IF 16.3 1区医学

Science Immunology Pub Date : 2026-05-08

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Monocyte-derived macrophages drive neurological tissue damage through mitochondrial reactive oxygen species 单核细胞来源的巨噬细胞通过线粒体活性氧驱动神经组织损伤

IF 16.3 1区医学

Science Immunology Pub Date : 2026-05-08

Juan Villar-Vesga, Donatella De Feo, Pauline Clément, Viola Bugada, Elèni Meuffels, Hannah Van Hove, Mitchell Bijnen, James King, Sophie Grundschober, Can Ulutekin, Maria Pena-Francesch, Sara Costa-Pereira, Laura Oberbichler, Violetta Gogoleva, Jeanne Kim, Katarina Wendy Schmidt, Musadiq A. Bhat, Deborah Greis, Frauke Seehusen, Francesco Prisco, Urvashi Dalvi, Dietmar Benke, Bettina Schreiner, Tommaso Patriachi, Florian Ingelfinger, Isabelle C. Arnold, Christian Münz, Melanie Greter, Aiman S. Saab, Burkhard Becher, Sarah Mundt

{"title":"Monocyte-derived macrophages drive neurological tissue damage through mitochondrial reactive oxygen species","authors":"Juan Villar-Vesga, Donatella De Feo, Pauline Clément, Viola Bugada, Elèni Meuffels, Hannah Van Hove, Mitchell Bijnen, James King, Sophie Grundschober, Can Ulutekin, Maria Pena-Francesch, Sara Costa-Pereira, Laura Oberbichler, Violetta Gogoleva, Jeanne Kim, Katarina Wendy Schmidt, Musadiq A. Bhat, Deborah Greis, Frauke Seehusen, Francesco Prisco, Urvashi Dalvi, Dietmar Benke, Bettina Schreiner, Tommaso Patriachi, Florian Ingelfinger, Isabelle C. Arnold, Christian Münz, Melanie Greter, Aiman S. Saab, Burkhard Becher, Sarah Mundt","doi":"","DOIUrl":"","url":null,"abstract":"<div >Reactive oxygen species (ROS) produced by mononuclear phagocytes (MPs) are widely believed to drive tissue damage in multiple sclerosis (MS), yet the distinct roles of central nervous system (CNS)–resident versus CNS-invading MPs remain unclear. Here, we combined single-cell profiling and conditional gene targeting to map and modulate ROS production across CNS MPs in a preclinical mouse model of MS. We show that monocyte-derived macrophages (MdMs) exhibit a higher oxidative stress gene signature and produce more ROS than microglia (Mglia). Challenging previous assumptions, our findings reveal that phagocytic NADPH oxidase 2 is dispensable for neuroinflammation. In contrast, quenching mitochondrial ROS (mtROS) through mitochondria-targeted catalase (mCAT) expression in MdMs, but not in Mglia, ameliorated disease severity in acute neuroinflammation. Although core phagocyte functions were unaltered in mCAT-expressing MdMs, our results demonstrate a direct neurotoxic role of mtROS. In sum, we identify MdMs as the primary driver of ROS-mediated oxidative neurological tissue damage.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 119","pages":""},"PeriodicalIF":16.3,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147830229","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