Giorgia Manni, Marco Gargaro, Doriana Ricciuti, Simona Fontana, Eleonora Padiglioni, Marco Cipolloni, Tommaso Mazza, Jessica Rosati, Alessandra di Veroli, Giulia Mencarelli, Benedetta Pieroni, Estevão Carlos Silva Barcelos, Giulia Scalisi, Francesco Sarnari, Alessandro di Michele, Luisa Pascucci, Francesca de Franco, Teresa Zelante, Cinzia Antognelli, Gabriele Cruciani, Vincenzo Nicola Talesa, Rita Romani, Francesca Fallarino
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引用次数: 0
摘要
树突状细胞(DC)是免疫反应的重要协调者,也是自身免疫性疾病免疫调节的潜在靶点。人类羊水分泌物组富含免疫调节因子,其中细胞外囊泡 (EV) 是重要的组成部分。然而,这些EVs对树突状细胞亚群的影响仍有待探索。在这项研究中,我们调查了高度纯化的树突状细胞亚群与羊水干细胞系衍生的EVs(HAFSC-EVs)之间的相互作用。我们的研究结果表明,HAFSC-EVs 通过 CD29 受体介导的内化作用,优先被传统的 2 型树突状细胞(cDC2)吸收,从而形成一种以减少表达和产生促炎介质为特征的耐受性 DC 表型。此外,在共培养系统中用HAFSC-EV处理cDC2细胞后,表达调节性T细胞标记物Foxp3的T细胞比例高于用药物处理的对照细胞。此外,将经 HAFSC-EV 处理的 cDC2 移植到 EAE 小鼠模型中,可抑制自身免疫反应并改善临床症状。这些结果表明,HAFSC-EV 可以作为一种很有前途的工具,将炎症性 cDC2 重编程为耐受表型,并控制中枢神经系统的自身免疫反应,是研究 EV 在 DC 亚群中的作用的潜在平台。
Amniotic fluid stem cell-derived extracellular vesicles educate type 2 conventional dendritic cells to rescue autoimmune disorders in a multiple sclerosis mouse model
Dendritic cells (DCs) are essential orchestrators of immune responses and represent potential targets for immunomodulation in autoimmune diseases. Human amniotic fluid secretome is abundant in immunoregulatory factors, with extracellular vesicles (EVs) being a significant component. However, the impact of these EVs on dendritic cells subsets remain unexplored. In this study, we investigated the interaction between highly purified dendritic cell subsets and EVs derived from amniotic fluid stem cell lines (HAFSC-EVs). Our results suggest that HAFSC-EVs are preferentially taken up by conventional dendritic cell type 2 (cDC2) through CD29 receptor-mediated internalization, resulting in a tolerogenic DC phenotype characterized by reduced expression and production of pro-inflammatory mediators. Furthermore, treatment of cDC2 cells with HAFSC-EVs in coculture systems resulted in a higher proportion of T cells expressing the regulatory T cell marker Foxp3 compared to vehicle-treated control cells. Moreover, transfer of HAFSC-EV-treated cDC2s into an EAE mouse model resulted in the suppression of autoimmune responses and clinical improvement. These results suggest that HAFSC-EVs may serve as a promising tool for reprogramming inflammatory cDC2s towards a tolerogenic phenotype and for controlling autoimmune responses in the central nervous system, representing a potential platform for the study of the effects of EVs in DC subsets.
期刊介绍:
The Journal of Extracellular Vesicles is an open access research publication that focuses on extracellular vesicles, including microvesicles, exosomes, ectosomes, and apoptotic bodies. It serves as the official journal of the International Society for Extracellular Vesicles and aims to facilitate the exchange of data, ideas, and information pertaining to the chemistry, biology, and applications of extracellular vesicles. The journal covers various aspects such as the cellular and molecular mechanisms of extracellular vesicles biogenesis, technological advancements in their isolation, quantification, and characterization, the role and function of extracellular vesicles in biology, stem cell-derived extracellular vesicles and their biology, as well as the application of extracellular vesicles for pharmacological, immunological, or genetic therapies.
The Journal of Extracellular Vesicles is widely recognized and indexed by numerous services, including Biological Abstracts, BIOSIS Previews, Chemical Abstracts Service (CAS), Current Contents/Life Sciences, Directory of Open Access Journals (DOAJ), Journal Citation Reports/Science Edition, Google Scholar, ProQuest Natural Science Collection, ProQuest SciTech Collection, SciTech Premium Collection, PubMed Central/PubMed, Science Citation Index Expanded, ScienceOpen, and Scopus.