Sengprasert Panjana, Leearamwat Nitikorn, Ngarmukos Srihatach, Yuktananda Pongsak, Tanavalee Aree, Reantragoon Rangsima
Medical Microbiology Interdisciplinary Program, Graduate School, Chulalongkorn University, Bangkok, Thailand.
Immunology Division, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Clin Exp Rheumatol. 2022 Mar;40(3):596-607. doi: 10.55563/clinexprheumatol/hjzqfs. Epub 2021 Jun 8.
A central hallmark of osteoarthritis (OA) is cartilage destruction. Chondrocytes not only control cartilage metabolism, but are capable of immunogenic responses. The role of chondrocytes in the pathogenesis of OA is still unclear. In this study, we aimed to determine the immunological role of chondrocytes in response to proteoglycan aggrecan (PG) peptides.
Human chondrocytes were isolated from cartilage of knee OA patients undergoing knee arthroplasty and stimulated with proteoglycan aggrecan peptides in the presence of IFNγ. Antigen presentation markers, co-stimulatory molecules, cytokine production, gene expression and antigen presentation to T cells were evaluated.
Our results show that IFNγ was required for the expression of MHC class I and II. However, stimulation with PG peptides P16-31 and P263-280, but not P2379-2394, increased expression level of co-stimulatory molecules (CD80 and CD86) and IL-6, IL-8 and TNFα production. This upregulation was seen in chondrocytes to nearly comparable levels of professional antigen-presenting cells. A similar pattern of gene expression was observed between P16-31 and P263-280 peptide stimulation on chondrocytes and this was different from P2379-2394 peptide treatment. Co-culture with autologous T cells revealed signi cant proliferation of cells when stimulating with the P263-280 peptides.
Our study shows that human chondrocytes display unique features of antigen presentation. Their ability to process certain proteoglycan aggrecan peptides, in which these molecules are synthesised by the cartilage themselves render the possibility of a role for "self-antigens" in the immunopathogenesis of OA.
骨关节炎（OA）的一个核心特征是软骨破坏。软骨细胞不仅控制软骨代谢，还能够产生免疫原性反应。软骨细胞在OA发病机制中的作用仍不清楚。在本研究中，我们旨在确定软骨细胞对蛋白聚糖聚集蛋白聚糖（PG）肽反应的免疫作用。
从接受膝关节置换术的膝OA患者的软骨中分离出人软骨细胞，并在存在IFNγ的情况下用蛋白聚糖聚集蛋白聚糖肽刺激。评估抗原呈递标志物、共刺激分子、细胞因子产生、基因表达以及向T细胞的抗原呈递。
我们的结果表明，MHC I类和II类的表达需要IFNγ。然而，用PG肽P16 - 31和P263 - 280刺激，但不是P2379 - 2394，增加了共刺激分子（CD80和CD86）的表达水平以及IL - 6、IL - 8和TNFα的产生。这种上调在软骨细胞中可见，达到与专业抗原呈递细胞几乎相当的水平。在软骨细胞上，P16 - 31和P263 - 280肽刺激之间观察到类似的基因表达模式，这与P2379 - 2394肽处理不同。与自体T细胞共培养显示，用P263 - 280肽刺激时细胞有显著增殖。
我们的研究表明，人软骨细胞具有独特的抗原呈递特征。它们处理某些蛋白聚糖聚集蛋白聚糖肽的能力，其中这些分子由软骨自身合成，使得“自身抗原”在OA免疫发病机制中发挥作用成为可能。
