Neutrophil-derived vesicles control complement activation to facilitate inflammation resolution

IF 42.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Cell Pub Date : 2025-02-11 DOI:10.1016/j.cell.2025.01.021

Alan Y. Hsu, Qingxiang Huang, Xiong Pi, Jianing Fu, Krishnan Raghunathan, Laxman Ghimire, Arumugam Balasubramanian, Xuemei Xie, Hongbo Yu, Fabien Loison, Viraga Haridas, Jiali Zha, Fei Liu, Shin-young Park, Kamal Bagale, Qian Ren, Yuping Fan, Yi Zheng, Jose A. Cancelas, Li Chai, Hongbo R. Luo

{"title":"Neutrophil-derived vesicles control complement activation to facilitate inflammation resolution","authors":"Alan Y. Hsu, Qingxiang Huang, Xiong Pi, Jianing Fu, Krishnan Raghunathan, Laxman Ghimire, Arumugam Balasubramanian, Xuemei Xie, Hongbo Yu, Fabien Loison, Viraga Haridas, Jiali Zha, Fei Liu, Shin-young Park, Kamal Bagale, Qian Ren, Yuping Fan, Yi Zheng, Jose A. Cancelas, Li Chai, Hongbo R. Luo","doi":"10.1016/j.cell.2025.01.021","DOIUrl":null,"url":null,"abstract":"Although subsets with immunosuppressive properties exist, neutrophils are typically known for their pro-inflammatory role and pathogen clearance capabilities. Here, we reveal that neutrophils can paradoxically aid in resolving inflammation by actively producing anti-inflammatory extracellular vesicles. These large aging-neutrophil-derived vesicles (LAND-Vs) do not fit into classical vesicle categorizations due to their specific size, structure, or biogenesis pathway. They are protected from efferocytotic clearance by phagocytes due to surface “do not eat me” signals and accumulate in the resolution phase of inflammation. CD55 on LAND-Vs exerts a robust, sustained anti-inflammatory effect by inhibiting complement 3 convertase, thereby reducing neutrophil recruitment and tissue damage. CD55<sup>+</sup> LAND-Vs originate in ordered lipid raft domains, where CD55 accumulates asymmetrically during neutrophil aging, and are subsequently formed through RhoA-dependent budding. Collectively, LAND-V emerges as a pivotal physiological immunomodulator and showcases functions that transcend the limited lifespan of neutrophils, offering a therapeutic target for inflammatory and infectious diseases.","PeriodicalId":9656,"journal":{"name":"Cell","volume":"52 1","pages":""},"PeriodicalIF":42.5000,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cell.2025.01.021","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Although subsets with immunosuppressive properties exist, neutrophils are typically known for their pro-inflammatory role and pathogen clearance capabilities. Here, we reveal that neutrophils can paradoxically aid in resolving inflammation by actively producing anti-inflammatory extracellular vesicles. These large aging-neutrophil-derived vesicles (LAND-Vs) do not fit into classical vesicle categorizations due to their specific size, structure, or biogenesis pathway. They are protected from efferocytotic clearance by phagocytes due to surface “do not eat me” signals and accumulate in the resolution phase of inflammation. CD55 on LAND-Vs exerts a robust, sustained anti-inflammatory effect by inhibiting complement 3 convertase, thereby reducing neutrophil recruitment and tissue damage. CD55⁺ LAND-Vs originate in ordered lipid raft domains, where CD55 accumulates asymmetrically during neutrophil aging, and are subsequently formed through RhoA-dependent budding. Collectively, LAND-V emerges as a pivotal physiological immunomodulator and showcases functions that transcend the limited lifespan of neutrophils, offering a therapeutic target for inflammatory and infectious diseases.

Abstract Image

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

中性粒细胞衍生的囊泡控制补体激活，促进炎症消退

虽然存在具有免疫抑制特性的亚群，但中性粒细胞通常以其促炎作用和病原体清除能力而闻名。在这里，我们揭示中性粒细胞可以矛盾地通过积极产生抗炎细胞外囊泡来帮助解决炎症。这些大的衰老中性粒细胞衍生囊泡（LAND-Vs）由于其特定的大小、结构或生物发生途径而不适合经典的囊泡分类。由于表面“不要吃我”的信号，它们受到保护，不被吞噬细胞清除，并在炎症的消退阶段积累。LAND-Vs上的CD55通过抑制补体3转化酶发挥强大、持续的抗炎作用，从而减少中性粒细胞募集和组织损伤。CD55+ land - v起源于有序的脂筏结构域，CD55在中性粒细胞老化过程中不对称积累，随后通过rhoa依赖性出芽形成。总之，LAND-V作为一种关键的生理免疫调节剂出现，并展示了超越中性粒细胞有限寿命的功能，为炎症和感染性疾病提供了治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Cell 生物-生化与分子生物学

CiteScore

110.00

自引率

0.80%

发文量

396

审稿时长

2 months

期刊介绍： Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO). The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries. In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.