Osteoarthritis (OA) is a degenerative disease that manifests as joint damage and synovial inflammation. To date, most studies have focused on the decrease in cartilage stiffness, chondrocyte viability, and changes in matrix-degrading enzymes. With the exception of a few inflammatory cytokines and macrophages, the immune response in OA is poorly characterized, and the crosstalk of joint damage with T and B cells in local lymph nodes is unknown. Here, using an in vivo mouse model of mechanical loading of mouse tibia, we demonstrate that CD8+ T cells and subsets of CD4+ T cells, and not B cells, increase in the local lymph nodes and contribute to the progression of load-induced OA pathology. We demonstrate that T cell response is sex- and age-dependent. Mechanical loading of T cell knock-out mice that lack αβ T cell receptor carrying cells resulted in attenuation of both cartilage degradation and osteophyte formation in loaded joints, with a concomitant increase in γδ+ T cells. Restricting the migration of T cells in lymphoid tissues through the systemic treatment using Sphingosine-1-phosphate (S1P) inhibitor, decreased localization of T cells in synovium, and attenuated cartilage degradation. Our results lay the foundation of the role T cells play in the joint damage of load-induced OA and allude to the use of S1P inhibitors and T cell immunotherapies for slowing the progression of OA pathology.

中文翻译：

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T细胞介导负荷诱导的骨关节炎的进展

骨关节炎（OA）是一种退行性疾病，表现为关节损伤和滑膜炎症。迄今为止，大多数研究都集中在软骨硬度，软骨细胞活力的降低以及基质降解酶的改变上。除少数炎症细胞因子和巨噬细胞外，OA的免疫反应特征不清，局部淋巴结中T细胞和B细胞的关节损伤串扰尚不清楚。在这里，使用小鼠胫骨机械负荷的体内小鼠模型，我们证明了CD8 + T细胞和CD4 + T细胞（而不是B细胞）的子集在局部淋巴结中增加，并有助于负荷诱导的OA病理学进展。我们证明T细胞反应是性别和年龄依赖性。缺少携带αβT细胞受体的细胞的T细胞基因敲除小鼠的机械负荷导致负荷关节中软骨降解和骨赘形成的减弱，同时γδ+ T细胞随之增加。通过使用Sphingosine-1-phosphate（S1P）抑制剂进行全身性治疗，可限制T细胞在淋巴组织中的迁移，减少滑膜中T细胞的定位，并减轻软骨的降解。我们的结果奠定了T细胞在负荷诱导的OA的关节损伤中发挥作用的基础，并暗示了使用S1P抑制剂和T细胞免疫疗法来减缓OA病理学的进展。通过使用Sphingosine-1-phosphate（S1P）抑制剂进行全身性治疗，可限制T细胞在淋巴组织中的迁移，减少滑膜中T细胞的定位，并减轻软骨的降解。我们的结果奠定了T细胞在负荷诱导的OA的关节损伤中发挥作用的基础，并暗示了使用S1P抑制剂和T细胞免疫疗法来减缓OA病理学的进展。通过使用Sphingosine-1-phosphate（S1P）抑制剂进行全身性治疗，可限制T细胞在淋巴组织中的迁移，减少滑膜中T细胞的定位，并减轻软骨的降解。我们的结果奠定了T细胞在负荷诱导的OA的关节损伤中发挥作用的基础，并暗示了使用S1P抑制剂和T细胞免疫疗法来减缓OA病理学的进展。