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循环外泌体通过免疫调节蛋白参与自身免疫性甲状腺疾病的发病机制。

Circulating Exosome Involves in the Pathogenesis of Autoimmune Thyroid Diseases Through Immunomodulatory Proteins.

机构信息

Department of Endocrinology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China.

Department of Endocrinology, Zhongshan Hospital, Fudan University, Shanghai, China.

出版信息

Front Immunol. 2021 Nov 11;12:730089. doi: 10.3389/fimmu.2021.730089. eCollection 2021.

DOI:10.3389/fimmu.2021.730089
PMID:34867951
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8636008/
Abstract

Autoimmune thyroid diseases (AITDs) are chronic organ-specific autoimmune diseases, mainly including Graves' disease (GD) and Hashimoto's thyroiditis (HT). Exosomes, as extracellular vesicles, contain a variety of biologically active substances that play a role in information exchange, thereby affecting the occurrence and progression of diseases. However, it is unclear whether exosomes are involved in the pathogenesis of AITDs. In this study, the role of exosomes in AITDs was explored from a proteomics perspective. Plasma exosomes were isolated from 12 patients with GD, 10 patients with HT, and seven normal controls (NC). Protein profiles were detected using the data-independent acquisition (DIA) method and analyzed to investigate changes in plasma exosome proteins. In the setting of GD, 11 proteins were upregulated while 197 proteins were downregulated compared with healthy people. Among them, MAP1S (log FC = 4.669, = 0.009) and VAMP8 (log FC = 3.216, = 0.003) were the most significantly upregulated, and RSU1 (log FC = -6.797, = 0.001), ACTB (log FC = -4.795, < 0.001), and CXCL7 (log FC = -4.674, < 0.001) were the most significantly downregulated. In the cases of HT, HGFL (log FC = 2.766, = 0.001), FAK1 (log FC = 2.213, < 0.001), and PTN12 (log FC = 1.624, < 0.001) were significantly upregulated, while PSMF1 (log FC = -3.591, < 0.001), PXL2B (log FC = -2.622, = 0.001), and CYTM (log FC = -1.609, < 0.001) were the most downregulated. These differential proteins were mainly enriched in the immune system and metabolic system, indicating that plasma exosomes may play an important role in systemic immune imbalance in AITDs.

摘要

自身免疫性甲状腺疾病(AITDs)是慢性器官特异性自身免疫性疾病,主要包括格雷夫斯病(GD)和桥本甲状腺炎(HT)。外泌体作为细胞外囊泡,包含多种具有生物活性的物质,在信息交流中发挥作用,从而影响疾病的发生和发展。然而,外泌体是否参与 AITDs 的发病机制尚不清楚。在这项研究中,我们从蛋白质组学的角度探讨了外泌体在 AITDs 中的作用。从 12 例 GD 患者、10 例 HT 患者和 7 例正常对照者(NC)中分离血浆外泌体。采用数据非依赖性采集(DIA)方法检测蛋白质谱,并进行分析,以研究血浆外泌体蛋白的变化。在 GD 中,与健康人相比,有 11 种蛋白上调,197 种蛋白下调。其中,MAP1S(logFC=4.669, =0.009)和 VAMP8(logFC=3.216, =0.003)上调最显著,RSU1(logFC=-6.797, =0.001)、ACTB(logFC=-4.795, <0.001)和 CXCL7(logFC=-4.674, <0.001)下调最显著。在 HT 中,HGFL(logFC=2.766, =0.001)、FAK1(logFC=2.213, <0.001)和 PTN12(logFC=1.624, <0.001)上调最显著,而 PSMF1(logFC=-3.591, <0.001)、PXL2B(logFC=-2.622, =0.001)和 CYTM(logFC=-1.609, <0.001)下调最显著。这些差异蛋白主要富集在免疫系统和代谢系统中,表明血浆外泌体可能在 AITDs 中的全身免疫失衡中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6af5/8636008/f5685ea2d313/fimmu-12-730089-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6af5/8636008/b0087ea9176a/fimmu-12-730089-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6af5/8636008/d121719ecfdf/fimmu-12-730089-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6af5/8636008/f5685ea2d313/fimmu-12-730089-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6af5/8636008/b0087ea9176a/fimmu-12-730089-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6af5/8636008/d121719ecfdf/fimmu-12-730089-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6af5/8636008/f5685ea2d313/fimmu-12-730089-g003.jpg

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