First Affiliated Hospital of Fujian Medical University, Fuzhou 350004, China.
Department of Allied Health Sciences, University of Connecticut, Storrs, CT 06269, USA.
Int J Mol Sci. 2023 Sep 7;24(18):13772. doi: 10.3390/ijms241813772.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease distinguished by synovial hyperplasia and a progressive destruction of joints. T cells are critical players in the pathogenesis of RA. We have previously identified a novel immune checkpoint molecule, TAPBPL, that inhibits T cell functions in vitro. As a model for human RA, we investigated the ability of the TAPBPL protein to ameliorate collagen type II (CII)-induced arthritis (CIA) in mice that were injected with recombinant TAPBPL or a control protein. The mice were analyzed for CIA development, immune cells, and their responses. We found that TAPBPL protein significantly decreased CIA incidence and reduced clinical and pathological arthritis scores, which were related to a lower number of activated CD4 T cells but a greater number of regulatory T cells (Tregs) in the spleen, and a reduction of Th1/Th17 inflammatory cytokines in the joints and serum. Importantly, TAPBPL protein inhibited CII-specific T cell growth and Th1 and Th17 cytokine expression and reduced the production of CII autoantibodies in the serum. Our results suggest that TAPBPL protein can ameliorate CIA in mice and has the potential to be used in the treatment of patients with RA.
类风湿关节炎（RA）是一种慢性炎症性自身免疫性疾病，其特征为滑膜增生和关节进行性破坏。T 细胞是 RA 发病机制中的关键参与者。我们之前已经鉴定出一种新型免疫检查点分子 TAPBPL，它可以在体外抑制 T 细胞功能。作为人类 RA 的模型，我们研究了重组 TAPBPL 或对照蛋白注射后 TAPBPL 蛋白对胶原诱导型关节炎（CIA）小鼠的缓解作用。分析了 CIA 发展、免疫细胞及其反应。我们发现 TAPBPL 蛋白显著降低 CIA 发生率，并降低临床和病理关节炎评分，这与脾脏中活化的 CD4 T 细胞数量减少但调节性 T 细胞（Treg）数量增加以及关节和血清中 Th1/Th17 炎症细胞因子减少有关。重要的是，TAPBPL 蛋白抑制了 CII 特异性 T 细胞的生长以及 Th1 和 Th17 细胞因子的表达，并减少了血清中 CII 自身抗体的产生。我们的结果表明，TAPBPL 蛋白可以改善 CIA 小鼠的病情，并有潜力用于治疗 RA 患者。
