Mohd Noor Nur Azira, Jun Quan Ng, Mazlan Nur Ainn Adabiah Adibah, Nurul Asma Abdullah, Ahmad Mohd Zain Muhammad Rajaei, Azlan Maryam
School of Health Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia.
Department of Orthopaedics, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia.
Immunol Invest. 2025 Apr;54(3):352-367. doi: 10.1080/08820139.2024.2443244. Epub 2024 Dec 19.
Exosomes can be found in the synovial fluid of inflamed knee joints, which play a significant role in osteoarthritis (OA) progression. However, their role - in modulating the cellular environment within the body, particularly monocytes remain unexplored. This study aimed to evaluate the immunomodulatory effect of exosomes on monocytes.
Exosomes were isolated by ultracentrifugation and characterized using nanoparticle tracking analysis (NTA), scanning electron microscopy (SEM), and Western blot. The effect of exosomes in modulating monocyte phenotypes as well as cytokine secretion were further assessed in a co-culture condition using flow cytometry and ELISA accordingly.
Exosomes were identified as spherical particles with a size distribution ranging from 30 nm to 150 nm. These nanoparticles intensely expressed exosome protein markers including CD9, CD63, CD81, and HSP70. The expression of HLA-DR, CD14, and CD11b on monocytes decreased in the presence of exosomes after 24 h of incubation, regardless of the dose. Exosomes significantly induced the release of anti-inflammatory cytokines IL-1Ra in a time- and dose-dependent manner, while TNF-α secretion remains unchanged regardless of the presence or absence of exosomes.
This study highlights the immunoregulatory role of exosomes on monocytes, emphasizing the need for further studies into the underlying mechanism.
在外伤性膝关节的滑液中可发现外泌体，其在骨关节炎（OA）进展中起重要作用。然而，它们在调节体内细胞环境，特别是单核细胞方面的作用仍未得到探索。本研究旨在评估外泌体对单核细胞的免疫调节作用。
通过超速离心分离外泌体，并使用纳米颗粒跟踪分析（NTA）、扫描电子显微镜（SEM）和蛋白质印迹法进行表征。相应地，使用流式细胞术和酶联免疫吸附测定法（ELISA）在共培养条件下进一步评估外泌体在调节单核细胞表型以及细胞因子分泌方面的作用。
外泌体被鉴定为球形颗粒，大小分布范围为30nm至150nm。这些纳米颗粒强烈表达外泌体蛋白标志物，包括CD9、CD63、CD81和热休克蛋白70（HSP70）。孵育24小时后，无论剂量如何，在外泌体存在的情况下，单核细胞上HLA-DR、CD14和CD11b的表达均降低。外泌体以时间和剂量依赖性方式显著诱导抗炎细胞因子白细胞介素-1受体拮抗剂（IL-1Ra）的释放，而无论是否存在外泌体，肿瘤坏死因子-α（TNF-α）的分泌均保持不变。
本研究强调了外泌体对单核细胞的免疫调节作用，强调需要进一步研究其潜在机制。
