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间充质干细胞及其外泌体通过恢复促炎效应T细胞和调节性T细胞之间的平衡来减轻骨关节炎。

Mesenchymal stem cells and their exosomes mitigate osteoarthritis by restoring the balance between proinflammatory Teffs and Tregs.

作者信息

Liu Tianhao, Ran Chunxiao, Zhao Dewei, Yang Fan, Guo Qiang, Yang Jiahui, Zhang Xiuzhi

机构信息

Zhongshan Clinical College, Dalian University, Dalian, Liaoning, China.

Department of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China.

出版信息

Front Aging. 2024 Nov 19;5:1509014. doi: 10.3389/fragi.2024.1509014. eCollection 2024.

Abstract

Osteoarthritis (OA) is a degenerative joint disease caused by chronic inflammation that damages articular cartilage. In addition to the wear and tear of joints, aberrant remodelling driven by a significant presence of inflammatory mediators within the joint is one of the key mechanisms in the pathogenesis of OA. Among these factors, hyperactivation of Teffs subsets plays a crucial role in promoting this pathological process. The immune imbalance between proinflammatory CD4 effector T cells (proinflammatory Teffs) and Tregs could be a crucial factor in the pathogenesis of OA. Therefore, correcting the imbalance of Tregs/proinflammatory Teffs may slow or inhibit the occurrence and development of OA, which could be a potential target for the treatment of OA. Mesenchymal stem cells (MSCs) possess anti-inflammatory and immunomodulatory properties, regulating both adaptive and innate immunity through mechanisms involving soluble factors such as IDO, PGE2, and TGF-β, as well as cell-to-cell contact and exosomes. Correcting the imbalance between Tregs and proinflammatory Teffs may be one of the mechanisms of MSCs in the treatment of OA. Therefore, this review aims to summarize the relationship between OA and the immune imbalance between Tregs and proinflammatory Teffs, the immunoregulatory role of Tregs in OA, and the role of MSCs and their exosomes in correcting the imbalance between Tregs and proinflammatory Teffs.

摘要

骨关节炎(OA)是一种由慢性炎症引起的退行性关节疾病,会损害关节软骨。除了关节磨损外,关节内大量炎症介质驱动的异常重塑是OA发病机制的关键机制之一。在这些因素中,效应性T细胞(Teffs)亚群的过度活化在促进这一病理过程中起关键作用。促炎CD4效应性T细胞(促炎性Teffs)与调节性T细胞(Tregs)之间的免疫失衡可能是OA发病机制中的一个关键因素。因此,纠正Tregs/促炎性Teffs的失衡可能会减缓或抑制OA的发生和发展,这可能是OA治疗的一个潜在靶点。间充质干细胞(MSCs)具有抗炎和免疫调节特性,通过涉及吲哚胺2,3-双加氧酶(IDO)、前列腺素E2(PGE2)和转化生长因子-β(TGF-β)等可溶性因子以及细胞间接触和外泌体的机制来调节适应性免疫和固有免疫。纠正Tregs与促炎性Teffs之间的失衡可能是MSCs治疗OA的机制之一。因此,本综述旨在总结OA与Tregs和促炎性Teffs之间的免疫失衡的关系、Tregs在OA中的免疫调节作用以及MSCs及其外泌体在纠正Tregs和促炎性Teffs之间失衡中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7794/11611854/84fa470463e5/fragi-05-1509014-g001.jpg

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