Abstract：
Members of the T-cell immunoglobulin and mucin (TIM) family, which is crucial for T-cell function, are implicated in autoimmunity. TIM-1 and -3 play distinct roles in autoimmunity, with TIM-1 acting as a costimulatory molecule and TIM-3 regulating Th1 responses. We investigated the therapeutic potential of anti-TIM-1 (RMT1-10) and anti-TIM-3 (RMT3-23) antibodies in an autoimmune arthritis model. Zymosan A was used to induce arthritis in female SKG mice. The arthritis scores, histology, mRNA expression, cytokine levels, micro-CT, and flow cytometry results were obtained. The application of RMT1-10 reduced the arthritis scores, histological damage, and CD4+T cell infiltrations, and it suppressed interleukin (IL)-6 and -17A and reduced TIM-3 mRNA expressions. RMT3-23 also lowered arthritis severity, improved histology, and reduced serum levels of tumor necrosis factor (TNF)-α and IL-17A. RMT3-23 inhibited intracellular TNF-α and IL-6 and early apoptosis. An amelioration of autoimmune arthritis was achieved by blocking the TIM-1 and -3 signaling pathways via RMT1-10 and RMT3-23 administration, leading to a widespread decrease in inflammatory cytokines. Both antibodies exhibited therapeutic effects, suggesting TIM-1 and -3 as potential targets for rheumatoid arthritis.
摘要：
T细胞免疫球蛋白和粘蛋白（TIM）家族的成员，这对T细胞功能至关重要，与自身免疫有关.TIM-1和-3在自身免疫中起着不同的作用，TIM-1作为共刺激分子和TIM-3调节Th1反应。我们研究了抗TIM-1（RMT1-10）和抗TIM-3（RMT3-23）抗体在自身免疫性关节炎模型中的治疗潜力。用酵母聚糖A诱导雌性SKG小鼠的关节炎。关节炎评分,组织学,mRNA表达，细胞因子水平，Micro-CT,并获得流式细胞术结果。RMT1-10的应用降低了关节炎评分，组织学损伤，和CD4+T细胞浸润，它抑制白细胞介素（IL）-6和-17A并降低TIM-3mRNA的表达。RMT3-23也降低了关节炎的严重程度，改善组织学，并降低血清肿瘤坏死因子（TNF）-α和IL-17A的水平。RMT3-23抑制细胞内TNF-α和IL-6以及早期凋亡。自身免疫性关节炎的改善是通过RMT1-10和RMT3-23给药阻断TIM-1和-3信号通路，导致炎性细胞因子的广泛减少。两种抗体都表现出治疗效果，提示TIM-1和-3是类风湿性关节炎的潜在靶标。
