SNX17 Regulates Antigen Internalisation and Phagosomal Maturation by Dendritic Cells.

IF 4.9 3区医学 Q2 IMMUNOLOGY Immunology Pub Date : 2024-11-19 DOI:10.1111/imm.13878

Sofía Dinamarca, Cristina Croce, Anna Salvioni, Facundo Garrido, Sandra Estrada Fidalgo, Gonzalo Bigliani, Luis S Mayorga, Nicolas Blanchard, Ignacio Cebrian

{"title":"SNX17 Regulates Antigen Internalisation and Phagosomal Maturation by Dendritic Cells.","authors":"Sofía Dinamarca, Cristina Croce, Anna Salvioni, Facundo Garrido, Sandra Estrada Fidalgo, Gonzalo Bigliani, Luis S Mayorga, Nicolas Blanchard, Ignacio Cebrian","doi":"10.1111/imm.13878","DOIUrl":null,"url":null,"abstract":"<p><p>Antigen cross-presentation is the process whereby small peptides derived from exogenous antigens are attached to MHC-I molecules triggering CD8+ T lymphocyte activation. The endocytic route of dendritic cells (DCs) is highly specialised for cross-presentation to initiate cytotoxic immune responses against numerous intracellular pathogens and tumours. In this study, we identify the endosomal protein sorting nexin (SNX) 17 as a key regulator of antigen internalisation and cross-presentation by DCs. SNX17 expression in DCs guarantees optimal cross-presentation of soluble, particulate, and Toxoplasma gondii-associated antigens. The silencing of SNX17 expression in DCs significantly affected the internalisation of exogenous antigens by fluid-phase endocytosis, phagocytosis, and more strikingly, T. gondii invasion. We show that SNX17 controls proper integrin recycling, actin cytoskeleton organisation, and phagosomal maturation. Altogether, our findings provide compelling evidence that SNX17 plays a central role in the modulation of the DC endocytic network, which is essential for competent antigen cross-presentation.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":4.9000,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/imm.13878","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Antigen cross-presentation is the process whereby small peptides derived from exogenous antigens are attached to MHC-I molecules triggering CD8+ T lymphocyte activation. The endocytic route of dendritic cells (DCs) is highly specialised for cross-presentation to initiate cytotoxic immune responses against numerous intracellular pathogens and tumours. In this study, we identify the endosomal protein sorting nexin (SNX) 17 as a key regulator of antigen internalisation and cross-presentation by DCs. SNX17 expression in DCs guarantees optimal cross-presentation of soluble, particulate, and Toxoplasma gondii-associated antigens. The silencing of SNX17 expression in DCs significantly affected the internalisation of exogenous antigens by fluid-phase endocytosis, phagocytosis, and more strikingly, T. gondii invasion. We show that SNX17 controls proper integrin recycling, actin cytoskeleton organisation, and phagosomal maturation. Altogether, our findings provide compelling evidence that SNX17 plays a central role in the modulation of the DC endocytic network, which is essential for competent antigen cross-presentation.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

SNX17 调控树突状细胞的抗原内化和吞噬体成熟

抗原交叉呈递是指来自外源性抗原的小肽附着在 MHC-I 分子上引发 CD8+ T 淋巴细胞活化的过程。树突状细胞（DCs）的内吞途径高度专业化，用于交叉呈递，启动针对多种细胞内病原体和肿瘤的细胞毒性免疫反应。在这项研究中，我们发现内泌体蛋白分选蛋白（SNX）17 是 DCs 抗原内化和交叉呈递的关键调节因子。SNX17在DC中的表达保证了可溶性、颗粒状和弓形虫相关抗原的最佳交叉呈递。抑制 SNX17 在直流细胞中的表达会显著影响外源抗原通过液相内吞、吞噬作用的内化，更显著的是会影响弓形虫的入侵。我们的研究表明，SNX17 控制着整合素的正常循环、肌动蛋白细胞骨架的组织以及吞噬体的成熟。总之，我们的研究结果提供了令人信服的证据，证明 SNX17 在调节 DC 内细胞网络中发挥着核心作用，而 DC 内细胞网络对有效的抗原交叉呈递至关重要。

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

Immunology 医学-免疫学

CiteScore

11.90

自引率

1.60%

发文量

175

审稿时长

4-8 weeks

期刊介绍： Immunology is one of the longest-established immunology journals and is recognised as one of the leading journals in its field. We have global representation in authors, editors and reviewers. Immunology publishes papers describing original findings in all areas of cellular and molecular immunology. High-quality original articles describing mechanistic insights into fundamental aspects of the immune system are welcome. Topics of interest to the journal include: immune cell development, cancer immunology, systems immunology/omics and informatics, inflammation, immunometabolism, immunology of infection, microbiota and immunity, mucosal immunology, and neuroimmunology. The journal also publishes commissioned review articles on subjects of topical interest to immunologists, and commissions in-depth review series: themed sets of review articles which take a 360° view of select topics at the heart of immunological research.

期刊最新文献

LGR4 Deficiency Aggravates Skin Inflammation and Epidermal Hyperplasia in Imiquimod-Induced Psoriasis. SNX17 Regulates Antigen Internalisation and Phagosomal Maturation by Dendritic Cells. Metabolic Regulation of Inflammation: Exploring the Potential Benefits of Itaconate in Autoimmune Disorders. Issue Information Coexistence of IL12Rβ1 and BTK Mutations in a Family.