Science Immunology最新文献_第3页

Platelet-derived serotonin drives age-related lung pathology in SARS-CoV-2 infection 血小板衍生的血清素驱动SARS-CoV-2感染中与年龄相关的肺部病理

IF 16.4 1区医学

Science Immunology Pub Date : 2026-08-28 DOI: 10.1126/sciimmunol.aec9853

Davide Marotta, Chiara Perucchini, Marta Grillo, Valeria Fumagalli, Pietro Di Lucia, Jordan Rixon, Micol Ravà, Leonardo Giustini, Chiara Malpighi, Giulia D’Uonnolo, Mariangela Scavone, Violette Mouro, Caitlin Abbott, Natalia Stachura-Chyla, Francesco Andreata, Erica Scalambrino, Marigrazia Clerici, Lorena Donnici, Marika Longo Minnolo, Donato Inverso, Raffaele De Francesco, Mauro Gaya, Zaverio M. Ruggeri, Armando Tripodi, Gian Marco Podda, Luca G. Guidotti, Matteo Iannacone, Marco De Giovanni

{"title":"Platelet-derived serotonin drives age-related lung pathology in SARS-CoV-2 infection","authors":"Davide Marotta, Chiara Perucchini, Marta Grillo, Valeria Fumagalli, Pietro Di Lucia, Jordan Rixon, Micol Ravà, Leonardo Giustini, Chiara Malpighi, Giulia D’Uonnolo, Mariangela Scavone, Violette Mouro, Caitlin Abbott, Natalia Stachura-Chyla, Francesco Andreata, Erica Scalambrino, Marigrazia Clerici, Lorena Donnici, Marika Longo Minnolo, Donato Inverso, Raffaele De Francesco, Mauro Gaya, Zaverio M. Ruggeri, Armando Tripodi, Gian Marco Podda, Luca G. Guidotti, Matteo Iannacone, Marco De Giovanni","doi":"10.1126/sciimmunol.aec9853","DOIUrl":"10.1126/sciimmunol.aec9853","url":null,"abstract":"<div >Elderly individuals affected by COVID-19 are vulnerable to severe respiratory failure for reasons that have remained poorly defined. Here, we show that platelet-released serotonin drives lung pathology in a mouse model of age-associated disease severity after SARS-CoV-2 infection. In middle-aged mice and aged human healthy donors, platelet serotonin release upon activation was enhanced, and increased morbidity with respiratory dysfunction was associated with activated platelets aggregating and promoting fibrin deposition in the lung microvasculature. Pharmacologic or genetic disruption of serotonin uptake, or blockade of serotonin-dependent signaling, attenuated platelet activation and protected against respiratory distress, independently of viral replication and immune responses. Inhibition of fibrin formation similarly reduced disease severity, implicating serotonin-driven platelet procoagulant activity as a key contributor to age-related lung dysfunction. Thus, serotonin-mediated platelet procoagulant activity is a major contributor to respiratory insufficiency during SARS-CoV-2 infection and a potential therapeutic target for preserving pulmonary function, particularly in the elderly.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 122","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.aec9853","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838457","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

Type I IFN–induced IFN-γ instructs monocyte-mediated systemic bacterial protection during type 2 intestinal helminth infection I型IFN诱导的IFN-γ在2型肠道蠕虫感染期间指导单核细胞介导的全身细菌保护

IF 16.4 1区医学

Science Immunology Pub Date : 2026-08-28 DOI: 10.1126/sciimmunol.aeh4719

Kelly Wemyss, Lauren M. Webb, Hayley M. Bridgeman, Ian E. Prise, Rufus H. Daw, Verena Kästele, Tovah N. Shaw, Sabrina Tamburrano, Seona Thompson, Elia D. Tait Wojno, Pedro H. Papotto, Richard K. Grencis, Andrew S. MacDonald, Jennifer S. Cavet, Joanne E. Konkel, Kathryn J. Else, John R. Grainger

{"title":"Type I IFN–induced IFN-γ instructs monocyte-mediated systemic bacterial protection during type 2 intestinal helminth infection","authors":"Kelly Wemyss, Lauren M. Webb, Hayley M. Bridgeman, Ian E. Prise, Rufus H. Daw, Verena Kästele, Tovah N. Shaw, Sabrina Tamburrano, Seona Thompson, Elia D. Tait Wojno, Pedro H. Papotto, Richard K. Grencis, Andrew S. MacDonald, Jennifer S. Cavet, Joanne E. Konkel, Kathryn J. Else, John R. Grainger","doi":"10.1126/sciimmunol.aeh4719","DOIUrl":"10.1126/sciimmunol.aeh4719","url":null,"abstract":"<div >Alterations to monocyte output and function occur during infections driving T helper 1 (T<sub>H</sub>1)–type inflammation. The degree to which monocytes respond to infections initiating alternative types of responses is poorly understood. Here, we describe a distinct state of the monocyte compartment associated with type 2–polarizing intestinal helminths. Unexpectedly, the adapted monocyte state in a type 2 setting was associated with acquisition of an interferon (IFN) signature. This IFN-induced state provided helminth-infected animals with systemic protection against secondary bacterial infection and allowed for the development of effective type 2 immunity. This pathway of monocyte education was distinct from that in T<sub>H</sub>1 settings and involved an endogenous bacteria–mediated induction of type I IFN that led to adaptive lymphocyte–dependent IFN-γ priming of monocytes. These findings reveal an IFN-driven mechanism of monocyte education that enables the host to be simultaneously protected against type 2 infections at barrier sites and type 1 infections in the circulation.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 122","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838456","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

Androgen signaling via sympathetic neurons regulates allergic pulmonary inflammation 雄性激素信号通过交感神经元调节过敏性肺部炎症

IF 16.4 1区医学

Science Immunology Pub Date : 2026-08-21 DOI: 10.1126/sciimmunol.aed0186

Xiaofan Tu, Hongjie Chen, Xiaoran Ma, Chantal Donovan, Jing Yang

引用次数: 0

CAR T cell–derived TNF is an early determinant of cytokine release syndrome severity CAR - T细胞衍生的TNF是细胞因子释放综合征严重程度的早期决定因素

IF 16.4 1区医学

Science Immunology Pub Date : 2026-08-21 DOI: 10.1126/sciimmunol.aea6276

Pieter L. Lindenbergh, Theodoros Giavridis, Ophélie Vivier, Michael A. Lopez, Anton Dobrin, Matthias Mack, José L. Cohen, Maria Themeli, Michel Sadelain

引用次数: 0

A dendritic cell autophagy–neutrophil axis limits intratumoral STING immunotherapy 树突状细胞自噬-中性粒细胞轴限制了肿瘤内STING免疫治疗

IF 16.4 1区医学

Science Immunology Pub Date : 2026-08-14 DOI: 10.1126/sciimmunol.adw6399

Adriana Loverre, Bakhos Jneid, Fabien Delisle, Magali Genest, Chantal Alkhoury, Konstantina Antoniadou, Nicolas Manel

{"title":"A dendritic cell autophagy–neutrophil axis limits intratumoral STING immunotherapy","authors":"Adriana Loverre, Bakhos Jneid, Fabien Delisle, Magali Genest, Chantal Alkhoury, Konstantina Antoniadou, Nicolas Manel","doi":"10.1126/sciimmunol.adw6399","DOIUrl":"10.1126/sciimmunol.adw6399","url":null,"abstract":"<div >The cyclic GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway promotes tumor immunogenicity, but intratumoral STING agonists, despite strong preclinical efficacy, have shown limited clinical efficacy. The mechanisms restricting therapeutic STING activation remain unclear. In mice, intratumoral delivery of the endogenous STING ligand cyclic guanosine monophosphate–adenosine monophosphate (GMP-AMP) (cGAMP) using viruslike particles (VLPs) preferentially activates STING in dendritic cells and primes circulating tumor-specific T cells. Using this system, we investigated mechanisms limiting effective STING-based immunotherapy. STING-induced type I interferon signaling was dispensable for cGAMP-VLP–mediated tumor control. In contrast, dendritic cell autophagy was required for generating circulating antitumor CD8 T cells and for regulating baseline neutrophil levels in lymph nodes. cGAMP-VLP overrode this regulation, inducing neutrophil accumulation in tumors and draining lymph nodes that limited efficacy. Neutrophil depletion enhanced tumor control through mechanisms involving neutrophil elastase and programmed cell death 1 ligand 1. These findings reveal that defective dendritic cell autophagy and neutrophil-mediated immunosuppression, rather than insufficient interferon signaling, hinder the effectiveness of intratumoral STING immunotherapy in preclinical mouse models.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 122","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148728672","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

Regulation of inflammation by oxidized lipids 氧化脂质调节炎症

IF 16.4 1区医学

Science Immunology Pub Date : 2026-08-14 DOI: 10.1126/sciimmunol.adv9397

Marco Di Gioia, Ivan Zanoni

{"title":"Regulation of inflammation by oxidized lipids","authors":"Marco Di Gioia, Ivan Zanoni","doi":"10.1126/sciimmunol.adv9397","DOIUrl":"10.1126/sciimmunol.adv9397","url":null,"abstract":"<div >Host-derived lipids undergoing enzymatic or nonenzymatic oxidation play critical roles in regulating inflammation. Polyunsaturated fatty acids, cholesterol, and cholesterol intermediates can be enzymatically oxidized and serve as signaling mediators controlling tissue homeostasis and immunity. Spontaneously generated oxidized lipids, including nonenzymatically oxidized phospholipids (oxPLs), result from oxidative stress and accumulate during inflammation, affecting cellular metabolism, immune cell functions, and cell fate. These distinct classes of oxidized lipids not only share overlapping inflammatory roles but also exhibit divergent effects depending on their molecular structures and cellular targets. This Review highlights the double-edged nature of oxPLs: Although their transient production triggers protective responses, their accumulation sustains inflammation, contributing to tissue damage. We also discuss the emerging roles of oxPLs in cell death programs, immune cell activation, and stromal cell functions, which are critical processes favoring tumor growth. Overall, we highlight how oxidized lipids orchestrate immune responses and explore their contribution to infectious diseases and cancer.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 122","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adv9397","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148728673","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

Fusion of IgG antibodies to albumin inhibits transport across the placenta 白蛋白IgG抗体融合抑制胎盘转运

IF 16.4 1区医学

Science Immunology Pub Date : 2026-08-14 DOI: 10.1126/sciimmunol.aee5151

Jeannette Nilsen, Kine M. K. Sand, Hana J. Al-Khabbaz, Lennart Maximilian van Ligtenberg, Simone Mester, Line Mathiesen, Hanna T. Noordzij, Kjell-Rune Jensen, Nils Leitzinger, Oda Ottersen, Sopisa Benjakul, Marie Leangen Herigstad, Fulgencio Ruso-Julve, Aina Karen Anthi, Anders Moen, Mari Nyquist-Andersen, Torleif Tollefsrud Gjølberg, Eirin Listau Bertelsen, Jason Cameron, Stian Foss, Gregory J. Christianson, Tilman Schlothauer, Tor Brynjar Stuge, Lisbeth E. Knudsen, Inger Sandlie, Derry C. Roopenian, Maria Therese Ahlen, Jan Terje Andersen

{"title":"Fusion of IgG antibodies to albumin inhibits transport across the placenta","authors":"Jeannette Nilsen, Kine M. K. Sand, Hana J. Al-Khabbaz, Lennart Maximilian van Ligtenberg, Simone Mester, Line Mathiesen, Hanna T. Noordzij, Kjell-Rune Jensen, Nils Leitzinger, Oda Ottersen, Sopisa Benjakul, Marie Leangen Herigstad, Fulgencio Ruso-Julve, Aina Karen Anthi, Anders Moen, Mari Nyquist-Andersen, Torleif Tollefsrud Gjølberg, Eirin Listau Bertelsen, Jason Cameron, Stian Foss, Gregory J. Christianson, Tilman Schlothauer, Tor Brynjar Stuge, Lisbeth E. Knudsen, Inger Sandlie, Derry C. Roopenian, Maria Therese Ahlen, Jan Terje Andersen","doi":"10.1126/sciimmunol.aee5151","DOIUrl":"10.1126/sciimmunol.aee5151","url":null,"abstract":"<div >Immunoglobulin G (IgG)–based monoclonal antibodies are effective therapies for cancer, autoimmune diseases, and migraine. However, they are actively transported across the placenta by the neonatal Fc receptor (FcRn), limiting their use during pregnancy. Using mouse models and an ex vivo human placental perfusion system, we show that although FcRn binds albumin independently of IgG, albumin is not transported to the fetus in mice or across human placental tissue. Fusion of IgG to albumin markedly reduced transplacental transport in both models while preserving the prolonged plasma half-life conferred by FcRn. Similarly, fragment antigen–binding fragments fused to engineered albumin with enhanced FcRn binding showed minimal fetal exposure. In a mouse model of fetal and neonatal alloimmune thrombocytopenia, albumin fusion of an anti–human platelet antigen IgG reduced fetal antibody transfer and attenuated thrombocytopenia in the offspring. These findings identify albumin as an attractive fusion partner for biologics intended to minimize fetal exposure during pregnancy.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 122","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148728695","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

Mist-ical memory: The airway defenses induced by FluMist vaccination in adults 雾化记忆：成人流感疫苗诱导的气道防御。

IF 16.4 1区医学

Science Immunology Pub Date : 2026-08-07 DOI: 10.1126/sciimmunol.ael0169

Huzaifa Zohair, Priyadharshini Devarajan

引用次数: 0

PKM2 works “off the books” to drive effector T cell function in MS PKM2在MS中“暗箱操作”驱动效应T细胞功能。

IF 16.4 1区医学

Science Immunology Pub Date : 2026-08-07 DOI: 10.1126/sciimmunol.ael0168

Alexia Falle, Manu Rangachari

引用次数: 0

A genotype-first approach reveals the molecular basis of pyrin inflammasome activation 基因型优先的方法揭示了pyrin炎性体活化的分子基础

IF 16.4 1区医学

Science Immunology Pub Date : 2026-08-07 DOI: 10.1126/sciimmunol.aea0705

Naoya Iwata, Yoshihiko Kuchitsu, Atsushi Hijikata, Hirofumi Shibata, Masahiko Nishitani-Isa, Mariko Aoki, Kazushi Izawa, Hiroyuki Yoshitomi, Junko Takita, Hideki Ueno, Tomohiko Taguchi, Takahiro Yasumi, Yoshitaka Honda

{"title":"A genotype-first approach reveals the molecular basis of pyrin inflammasome activation","authors":"Naoya Iwata, Yoshihiko Kuchitsu, Atsushi Hijikata, Hirofumi Shibata, Masahiko Nishitani-Isa, Mariko Aoki, Kazushi Izawa, Hiroyuki Yoshitomi, Junko Takita, Hideki Ueno, Tomohiko Taguchi, Takahiro Yasumi, Yoshitaka Honda","doi":"10.1126/sciimmunol.aea0705","DOIUrl":"10.1126/sciimmunol.aea0705","url":null,"abstract":"<div >Mutations in the <i>MEFV</i> gene, which encodes pyrin, are associated with a spectrum of inflammatory conditions called pyrin-associated autoinflammatory diseases (PAADs). Of the 400 <i>MEFV</i> variants listed in the Infevers database, most are classified as variants of uncertain significance. Thus, genetic diagnosis of PAADs remains challenging, and the molecular mechanisms underlying pyrin activation remain poorly understood. Here, we used a cell-based pyroptosis assay to stratify 265 missense <i>MEFV</i> variants and identified previously uncharacterized pathogenic variants. We then characterized the interaction between the pyrin B30.2 domain and CDC42, a key regulator of pyrin intracellular trafficking and activation. We found that classical familial Mediterranean fever (FMF)–related variants bind tightly to CDC42 to induce pyrin hyperactivation, whereas certain non-FMF variants induce pyrin hyperactivation independently of CDC42, indicating involvement of multiple pathways in pyrin activation. Our approach provides a proof of concept for a genotype-first approach, which may advance our understanding of complex human diseases.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"11 122","pages":""},"PeriodicalIF":16.4,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148687813","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