外泌体作为自身免疫性炎症中的免疫调节剂:对原发性干燥综合征的意义。

Exosomes as immunomodulators in autoimmune inflammation: implications for primary Sjögren's disease.

作者信息

Hong Yanggang, Chen Siyan, Jiang Xiaoyang, Zhang Jinwen, Liang Xinyue, Yao Jiani, Gao Sheng, Hua Chunyan

机构信息

The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325035, Zhejiang Province, China.

School of Ophthalmology & Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, 325035, Zhejiang Province, China.

出版信息

Inflamm Res. 2025 Jun 13;74(1):91. doi: 10.1007/s00011-025-02053-0.

Abstract

Primary Sjögren's disease (pSD) is a systemic autoimmune disorder characterized by exocrine gland dysfunction and lymphocytic infiltration, leading to dry mouth and eyes. Increasing evidence implicates extracellular vesicles, particularly exosomes, as critical mediators of immune regulation in pSD. This review outlines the biogenesis, molecular composition, and immunomodulatory functions of exosomes, and summarizes their emerging roles in the pathogenesis, diagnosis, and potential treatment of pSD. Exosomes derived from immune and glandular cells carry diverse cargoes, such as miRNAs, proteins, and nucleic acids, that modulate disease-relevant immune pathways. For example, exosomal miR-BART13-3p from Epstein-Barr virus-infected B cells suppresses STIM1 and AQP5, impairing salivary gland function, while PD-L1-enriched exosomes from mesenchymal stem cells inhibit T follicular helper cell polarization via the PI3K/AKT pathway, thereby modulating B-cell activation. Additional exosomal cargoes affect Th17/Treg balance, inflammasome activation, and type I interferon signaling. We also highlight the diagnostic potential of disease-specific exosomal markers in plasma and discuss advances in preclinical studies using exosomes as therapeutic agents. However, significant challenges remain, including cargo heterogeneity, lack of standardized isolation methods, and limited clinical data, all of which hinder the translation of exosome-based therapies into clinical practice. By integrating mechanistic and translational findings, this review provides a comprehensive perspective on the immunological and clinical relevance of exosomes in pSD. These insights may guide future development of diagnostic biomarkers and targeted therapies in autoimmune diseases.

摘要

原发性干燥综合征(pSD)是一种全身性自身免疫性疾病,其特征为外分泌腺功能障碍和淋巴细胞浸润,导致口干和眼干。越来越多的证据表明,细胞外囊泡,尤其是外泌体,是pSD免疫调节的关键介质。本综述概述了外泌体的生物发生、分子组成和免疫调节功能,并总结了它们在pSD发病机制、诊断和潜在治疗中的新作用。源自免疫细胞和腺细胞的外泌体携带多种物质,如微小RNA、蛋白质和核酸,可调节与疾病相关的免疫途径。例如,来自爱泼斯坦-巴尔病毒感染的B细胞的外泌体miR-BART13-3p抑制基质相互作用分子1(STIM1)和水通道蛋白5(AQP5),损害唾液腺功能,而间充质干细胞中富含程序性死亡受体配体1(PD-L1)的外泌体通过磷脂酰肌醇-3-激酶/蛋白激酶B(PI3K/AKT)途径抑制滤泡辅助性T细胞极化,从而调节B细胞活化。其他外泌体物质影响辅助性T细胞17/调节性T细胞(Th17/Treg)平衡、炎性小体活化和I型干扰素信号传导。我们还强调了血浆中疾病特异性外泌体标志物的诊断潜力,并讨论了将外泌体用作治疗剂的临床前研究进展。然而,仍然存在重大挑战,包括物质异质性、缺乏标准化分离方法以及临床数据有限,所有这些都阻碍了基于外泌体的疗法转化为临床实践。通过整合机制和转化研究结果,本综述提供了关于外泌体在pSD中的免疫学和临床相关性的全面观点。这些见解可能会指导自身免疫性疾病诊断生物标志物和靶向治疗的未来发展。

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