T 细胞免疫球蛋白和粘蛋白 (TIM) 家族的成员对 T 细胞功能至关重要，与自身免疫有关。 TIM-1 和-3 在自身免疫中发挥着不同的作用，TIM-1 充当共刺激分子，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。酵母聚糖 A 用于诱导雌性 SKG 小鼠关节炎。获得关节炎评分、组织学、mRNA 表达、细胞因子水平、显微 CT 和流式细胞术结果。 RMT1-10的应用减少了关节炎评分、组织学损伤和CD4 T细胞浸润，并抑制白细胞介素(IL)-6和-17A并减少TIM-3 mRNA表达。 RMT3-23 还可以降低关节炎的严重程度、改善组织学并降低肿瘤坏死因子 (TNF)-α 和 IL-17A 的血清水平。 RMT3-23 抑制细胞内 TNF-α 和 IL-6 以及早期细胞凋亡。通过施用 RMT1-10 和 RMT3-23 阻断 TIM-1 和 -3 信号通路，从而改善炎症细胞因子，从而改善自身免疫性关节炎。两种抗体均表现出治疗效果，表明 TIM-1 和 -3 是类风湿性关节炎的潜在靶标。© 作者 2024。由牛津大学出版社代表英国免疫学会出版。版权所有。如需商业重复使用，请联系 reprints@oup.com 获取转载和转载的翻译权。所有其他权限均可通过我们网站文章页面上的“权限”链接通过我们的 RightsLink 服务获得 - 欲了解更多信息，请联系journals.permissions@oup.com。

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.© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.