Science Immunology最新文献_第2页

Fibrinoid-associated neutrophils promote invasive placentation and neutrophil reprogramming at the maternal-fetal interface 纤维蛋白相关的中性粒细胞促进侵入性胎盘和母胎界面的中性粒细胞重编程

IF 16.4 1区医学

Science Immunology Pub Date : 2026-09-25 DOI: 10.1126/sciimmunol.aea4118

Anna-Lena Höbler, Andreas Ian Lackner, Barbara Öhler, Laszlo Musiejovsky, Peter Haslinger, Sigrid Vondra, Theresa Maxian, Felix Kosta, Gudrun Meinhardt, Jasmin Wächter, Patricia Favaro, Daniel Ho, Trevor Bruce, Hanna Waldhäusl, Leila Saleh, Christian Fiala, Sandra Haider, Gernot Schabbauer, Martin Knöfler, Sean C. Bendall, Michael Angelo, Jürgen Pollheimer

{"title":"Fibrinoid-associated neutrophils promote invasive placentation and neutrophil reprogramming at the maternal-fetal interface","authors":"Anna-Lena Höbler, Andreas Ian Lackner, Barbara Öhler, Laszlo Musiejovsky, Peter Haslinger, Sigrid Vondra, Theresa Maxian, Felix Kosta, Gudrun Meinhardt, Jasmin Wächter, Patricia Favaro, Daniel Ho, Trevor Bruce, Hanna Waldhäusl, Leila Saleh, Christian Fiala, Sandra Haider, Gernot Schabbauer, Martin Knöfler, Sean C. Bendall, Michael Angelo, Jürgen Pollheimer","doi":"10.1126/sciimmunol.aea4118","DOIUrl":"10.1126/sciimmunol.aea4118","url":null,"abstract":"<div >Successful early pregnancy depends on coordinated interactions between the placenta and maternal immune cells, but the mechanisms underlying this interplay remain incompletely understood. Placenta-derived extravillous trophoblasts (EVTs) invade the decidua basalis and remodel maternal vessels, yet the contribution of neutrophils to this process is unclear. Here, we analyzed first-trimester human decidual tissue together with blood samples and identified decidual fibrinoid-associated neutrophils (dFANs) localized to Rohr’s layer, a fibrinoid matrix between the decidua proper and the intervillous space. Flow cytometry and mass cytometry showed that dFANs differ phenotypically from donor-matched peripheral blood neutrophils (PBNs). Functionally, dFANs secreted high levels of matrix metalloproteinase-9 (MMP-9) and promoted EVT invasion, whereas PBNs induced EVT apoptosis. dFAN-derived MMP-9 enhanced activation of latent transforming growth factor-β (TGF-β), which suppressed PBN cytotoxicity and shifted PBNs toward an MMP-9–hypersecretory, proinvasive state. These findings define a dFAN-dependent MMP-9–TGF-β axis that supports invasive placentation at the maternal-fetal interface.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 123","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035514","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

In vitro induction of human germinal center B cells 体外诱导人生发中心B细胞

IF 16.4 1区医学

Science Immunology Pub Date : 2026-09-18 DOI: 10.1126/sciimmunol.aeg5223

David G. Priest, Melike Fusun Demir, Wataru Ise, James B. Wing

{"title":"In vitro induction of human germinal center B cells","authors":"David G. Priest, Melike Fusun Demir, Wataru Ise, James B. Wing","doi":"10.1126/sciimmunol.aeg5223","DOIUrl":"10.1126/sciimmunol.aeg5223","url":null,"abstract":"<div >During antibody responses, germinal centers (GCs) act as a key site for somatic hypermutation (SHM) and affinity maturation of B cells. However, their lymphoid tissue localization has made experimental manipulation of human germinal center B (GCB) cells difficult. Here, we describe a simple in vitro method, modeling T cell–derived signaling, that converts human naive B cells into BCL6<sup>+</sup> induced GCB-like (iGCB) cells. Through side-by-side proteomic and transcriptional single-cell analysis of iGCB and human tonsil GCB cells, we show that iGCB cells recapitulate the surface marker, transcription factor, DNA repair, and glycosylation signatures that define human GCB cells and display ongoing activation-induced cytidine deaminase (AID)–dependent SHM. iGCB cells can be generated from naive B cells and from unswitched memory/circulating marginal zone cells but not class-switched memory B cells. Using this system, we define signals critical for human GCB formation and identify interventions that block their induction, providing a simple and manipulable model of human GCB cell biology.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 123","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.aeg5223","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148985057","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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Erratum for the Review “Regulation of inflammation by oxidized lipids” “氧化脂质调节炎症”综述的勘误

IF 16.4 1区医学

Science Immunology Pub Date : 2026-09-18 DOI: 10.1126/sciimmunol.aem1553

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In vivo CRISPR screens identify the glutamine transporter SLC1A5 as a metabolic barrier to antitumor immunity 体内CRISPR筛选鉴定谷氨酰胺转运体SLC1A5是抗肿瘤免疫的代谢屏障

IF 16.4 1区医学

Science Immunology Pub Date : 2026-09-18 DOI: 10.1126/sciimmunol.aea4179

Wenlong Jia, Guanxing Yu, Shenqi Han, Zhibo Ma, Junnan Liang, Wei Yan, Xinling Zhang, Chenglong Zeng, Lin Xue, Feng Xia, Ganxun Li, Ran Tao, Peixiang Lan, Wei Yan, Wanguang Zhang, Huifang Liang, Xiaoping Chen, Zhao Huang, Bixiang Zhang

{"title":"In vivo CRISPR screens identify the glutamine transporter SLC1A5 as a metabolic barrier to antitumor immunity","authors":"Wenlong Jia, Guanxing Yu, Shenqi Han, Zhibo Ma, Junnan Liang, Wei Yan, Xinling Zhang, Chenglong Zeng, Lin Xue, Feng Xia, Ganxun Li, Ran Tao, Peixiang Lan, Wei Yan, Wanguang Zhang, Huifang Liang, Xiaoping Chen, Zhao Huang, Bixiang Zhang","doi":"10.1126/sciimmunol.aea4179","DOIUrl":"10.1126/sciimmunol.aea4179","url":null,"abstract":"<div >Tumor cells often evade immune pressure via metabolic reprogramming, yet the key metabolic regulators orchestrating this process remain incompletely defined. Here, using in vivo metabolic CRISPR screening under distinct immune pressures, we identified tumor cell–intrinsic solute carrier family 1 member 5 (SLC1A5) as a metabolic node that sustains an immunosuppressive tumor microenvironment. SLC1A5-mediated glutamine metabolism in tumor cells modulated CD8 T cell infiltration and effector function, reshaping tumor responses to immune checkpoint blockade therapy. Glucose deprivation up-regulated SLC1A5 isoforms in tumor cells, enhancing glutamine uptake and glutathione synthesis. This adaptation limited mitochondrial oxidative stress and cytosolic mitochondrial DNA release, thereby suppressing cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS-STING) activation, interferon-β production, and CD8 T cell antitumor responses. These findings define a glutamine-fueled metabolic program as a barrier to tumor immunogenicity, positioning SLC1A5 as a tumor-intrinsic metabolic regulator with potential therapeutic relevance.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 123","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148985018","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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AMnESTI reverses age-associated lung immune decline to drive heterosubtypic protection by inactivated influenza vaccines amsti逆转年龄相关的肺部免疫衰退，驱动灭活流感疫苗的异亚型保护

IF 16.4 1区医学

Science Immunology Pub Date : 2026-09-11 DOI: 10.1126/sciimmunol.adz5242

Shilin Gao, Quanwei Zhang, Asmita Banstola, Haoran Lu, Zhengkun Zhang, Zhilong Wang, Mei. X. Wu

{"title":"AMnESTI reverses age-associated lung immune decline to drive heterosubtypic protection by inactivated influenza vaccines","authors":"Shilin Gao, Quanwei Zhang, Asmita Banstola, Haoran Lu, Zhengkun Zhang, Zhilong Wang, Mei. X. Wu","doi":"10.1126/sciimmunol.adz5242","DOIUrl":"10.1126/sciimmunol.adz5242","url":null,"abstract":"<div >Existing influenza vaccines fail to elicit heterosubtypic immunity and have limited efficacy in the elderly. We developed AMnESTI (AEC-targeting MN Encapsulated STING agonist), an alveolar epithelial cell (AEC)–targeting manganese-complexed liposome encapsulating the stimulator of interferon genes (STING) agonist ADU-S100. Intranasal administration activated the cyclic GMP-AMP synthase–STING pathway in AECs, robustly expanding plasmacytoid dendritic cells, monocyte-derived dendritic cells, and inflammatory monocytes while reducing regulatory T cells (T<sub>reg</sub> cells) and immunosuppressive cDC2β<sup>+</sup> cells and promoting M1 macrophage polarization. Single-cell RNA sequencing and flow cytometry established that the adjuvant sufficiently revived the aged lung immunity in mice to a proimmune state at the cellular, molecular, and functional levels, consistent with immune responses in younger mice. A single intranasal dose of AMnESTI-adjuvanted influenza vaccine conferred complete heterosubtypic protection in aged mice against representative influenza strains. These findings demonstrate that transient reprogramming of aged lung immunity facilitates robust vaccine responses and identify AECs as a potential mucosal adjuvant target for broadly protective influenza vaccines in the elderly.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 123","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922807","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

Adaptive motility enables neutrophils to rapidly navigate confined capillaries 适应性运动使中性粒细胞能够快速导航受限的毛细血管

IF 16.4 1区医学

Science Immunology Pub Date : 2026-09-04 DOI: 10.1126/sciimmunol.aea1426

Mathieu Deygas, Mathilde Bernard, Pierre Nivoit, Henry De Belly, Alexandre Deslys, Theresa Jakuszeit, Damien Cuvelier, Moira Garcia-Gomez, Lucie Barbier, Li Wang, Mathieu Maurin, Emmanuel Tejerina, Oumaima Baaziz, Emmanuel Terriac, Rafaele Attia, Anna Kniazeva, Serge Garbay, Marina Ortega-Zapero, Angela Saez, Raquel Gomez-Bris, Pilar Gonzalo, Jose M. Gonzalez-Granado, Vicente Andrés, Orion D. Weiner, Ana-Maria Lennon-Duménil, Guillaume Duménil, Matthieu Piel, Pablo Vargas

{"title":"Adaptive motility enables neutrophils to rapidly navigate confined capillaries","authors":"Mathieu Deygas, Mathilde Bernard, Pierre Nivoit, Henry De Belly, Alexandre Deslys, Theresa Jakuszeit, Damien Cuvelier, Moira Garcia-Gomez, Lucie Barbier, Li Wang, Mathieu Maurin, Emmanuel Tejerina, Oumaima Baaziz, Emmanuel Terriac, Rafaele Attia, Anna Kniazeva, Serge Garbay, Marina Ortega-Zapero, Angela Saez, Raquel Gomez-Bris, Pilar Gonzalo, Jose M. Gonzalez-Granado, Vicente Andrés, Orion D. Weiner, Ana-Maria Lennon-Duménil, Guillaume Duménil, Matthieu Piel, Pablo Vargas","doi":"10.1126/sciimmunol.aea1426","DOIUrl":"10.1126/sciimmunol.aea1426","url":null,"abstract":"<div >To reach inflamed tissues, neutrophils must traverse capillaries as narrow as 2 micrometers. However, how they do so without compromising blood flow or capillary function has remained unclear. By combining intravital live-cell imaging with biomimetic microdevices, we show that neutrophils maintain migration speed in capillaries across increasing levels of confinement. This behavior was not shared by other leukocytes and was independent of nuclear properties. Instead, confinement rapidly engaged Rho-dependent actomyosin contractility at the cell rear, thereby offsetting the increased mechanical resistance imposed by confinement. Disrupting this adaptive response caused neutrophil jamming and eventual occlusion of confined capillary-like networks. These findings identify a neutrophil-intrinsic mechanism that couples capillary confinement to rapid migratory adaptation, helping preserve vascular patency and potentially limiting tissue dysfunction during inflammation.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 123","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890199","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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Old dog with new tricks: SARS-CoV-2 variant–specific B cells complement imprinted memory 老狗有新花样：SARS-CoV-2变异特异性B细胞补充印迹记忆。

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Science Immunology Pub Date : 2026-09-04 DOI: 10.1126/sciimmunol.ael7920

Lauren B. Rodda

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The many roads to B cell memory 通往B细胞记忆的许多途径。

IF 16.4 1区医学

Science Immunology Pub Date : 2026-09-04 DOI: 10.1126/sciimmunol.ael7921

Oluwagbemiga A. Ojo, Stephanie C. Eisenbarth

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Tissue mitochondrial activity dictates the macrophage pool size 组织线粒体活性决定巨噬细胞池的大小

IF 16.4 1区医学

Science Immunology Pub Date : 2026-09-04 DOI: 10.1126/sciimmunol.aeb9244

Laura Pena-Couso, Jon Sicilia, Sofía Vieto, Roberto Silva-Rojas, María Sánchez-Díaz, Enrique Calvo, Rafael Romero-Becerra, Cintia Folgueira, Leticia Herrera-Melle, Raquel Justo-Méndez, Xiaotong Hong, Silvia Campanario, Juan A. López, Georgiana Crainiciuc, María Gil, Sandra Martín-Salamanca, Vera Lukesova, Jessica Segalés, Antonio L. Serrano, Iván Ballesteros, Marta León, Macarena de Andrés-Laguillo, Sebastian A. Stifter, Lorena Esteban-Martínez, Joan Isern, Jorge Alegre-Cebollada, Miguel Torres, Melanie Greter, Jesús Vázquez, José A. Enríquez, Guadalupe Sabio-Buzo, Pura Muñoz-Cánoves, Andrés Hidalgo, José A. Nicolás-Ávila

{"title":"Tissue mitochondrial activity dictates the macrophage pool size","authors":"Laura Pena-Couso, Jon Sicilia, Sofía Vieto, Roberto Silva-Rojas, María Sánchez-Díaz, Enrique Calvo, Rafael Romero-Becerra, Cintia Folgueira, Leticia Herrera-Melle, Raquel Justo-Méndez, Xiaotong Hong, Silvia Campanario, Juan A. López, Georgiana Crainiciuc, María Gil, Sandra Martín-Salamanca, Vera Lukesova, Jessica Segalés, Antonio L. Serrano, Iván Ballesteros, Marta León, Macarena de Andrés-Laguillo, Sebastian A. Stifter, Lorena Esteban-Martínez, Joan Isern, Jorge Alegre-Cebollada, Miguel Torres, Melanie Greter, Jesús Vázquez, José A. Enríquez, Guadalupe Sabio-Buzo, Pura Muñoz-Cánoves, Andrés Hidalgo, José A. Nicolás-Ávila","doi":"10.1126/sciimmunol.aeb9244","DOIUrl":"10.1126/sciimmunol.aeb9244","url":null,"abstract":"<div >Removal of cellular waste from the extracellular space is fundamental for tissue health. Because the rate of material ejected by parenchymal cells varies across tissues, we searched for mechanisms that couple waste production and removal. Here, we show that the uptake of parenchyma-released mitochondria by macrophages is prominent across organs that rely on oxidative respiration—including heart, skeletal muscle, and brown adipose tissue—and that macrophage numbers closely align with the mitochondrial activity of each of these organs. We found that the mitochondrial activity of myofibers dictates the abundance of macrophages by modulating colony-stimulating factor 1 (CSF1) availability and the number of CSF1-producing fibroblasts in the tissue. Consequently, inhibition of CSF1–CSF1 receptor (CSF1R) signaling depleted macrophages and collapsed the mitochondrial activity of skeletal muscles. We propose that, by coupling macrophage abundance to the mitochondrial activity of their parenchyma, tissues ensure efficient waste disposal and fitness.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 123","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890217","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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Positive selection of IgG over IgM plasma cells through BCR isotype–specific antigen presentation and signaling 通过BCR同型特异性抗原呈递和信号传导，IgG在IgM浆细胞上的阳性选择

IF 16.4 1区医学

Science Immunology Pub Date : 2026-09-04 DOI: 10.1126/sciimmunol.aee8841

Yuki Tai, Takuya Koike, Hiromi Yamamoto, Kyoko Shida, Niklas Engels, Takeshi Inoue, Wataru Ise, Jürgen Wienands, Tomohiro Kurosaki

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