Administration of Recombinant TAPBPL Protein Ameliorates Collagen-Induced Arthritis in Mice.
Administration of Recombinant TAPBPL Protein Ameliorates Collagen-Induced Arthritis in Mice.
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DOI：
10.3390/ijms241813772
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发表时间：
2023-09-07
影响因子：
5.6
通讯作者：
Lai L
中科院分区：
文献类型：
--
作者：
Zhang Z;Zhao J;Lai KC;Lai L
类风湿性关节炎（RA）是一种以滑膜增生和关节进行性破坏为特征的慢性炎症性自身免疫性疾病。T细胞是RA发病机制中的关键参与者。我们之前已经确定了一种新的免疫检查点分子TAPBPL，它在体外抑制T细胞功能。作为人RA的模型，我们研究了TAPBPL蛋白改善注射重组TAPBPL或对照蛋白的小鼠中II型胶原蛋白（CII）诱导的关节炎（CIA）的能力。分析小鼠的CIA发育、免疫细胞及其反应。我们发现，TAPBPL蛋白显着降低CIA的发病率，降低临床和病理性关节炎评分，这与活化的CD 4 T细胞的数量减少，但更多的调节性T细胞（T细胞）在脾脏，并减少Th 1/Th 17炎症细胞因子在关节和血清。重要的是，TAPBPL蛋白抑制CII特异性T细胞生长和Th 1和Th 17细胞因子表达，并减少血清中CII自身抗体的产生。我们的研究结果表明，TAPBPL蛋白可以改善小鼠CIA，并有可能用于治疗RA患者。
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.
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通讯作者：
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