Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
University Center for Health Science, Department of Molecular Biology and Genomics, University of Guada-lajara, Guadalajara, Jalisco, Mexico.
Scand J Immunol. 2024 Dec;100(6):e13410. doi: 10.1111/sji.13410. Epub 2024 Sep 27.
This study aimed to investigate the role of TSPAN32, a member of the tetraspanin family, in rheumatoid arthritis (RA). The objective was to assess the expression levels of TSPAN32 in experimental RA models and in RA patient immune cells, exploring its potential as a regulatory factor in RA pathogenesis. The study employed adjuvant-induced arthritis in rats and collagen-induced arthritis (CIA) in mice as experimental models. Ex vivo analyses included evaluating TSPAN32 expression in immune cells at different stages of the disease. In silico data analysis involved examining transcriptomic datasets from drug-naïve and treated RA patients to correlate TSPAN32 expression with clinical parameters. TSPAN32 overexpression experiments in splenocytes from CIA mice aimed to demonstrate its functional impact on antigen-specific immune responses. The animal models revealed a significant downregulation of TSPAN32, particularly in synovial-infiltrating T cells. Also, TSPAN32 overexpression inhibited pro-inflammatory cytokine production in splenocytes. In RA patients, TSPAN32 was consistently downregulated in circulating and synovial-infiltrating T cells, as well as in CD8+ T cells, B cells and NK cells. Drug treatment did not significantly alter TSPAN32 levels. Negative correlations were observed between TSPAN32 expression and inflammatory markers (CRP, ESR) and clinical scores (SDAI) in RA patients. This study suggests that reduced TSPAN32 expression characterizes pathogenic T-cell populations in RA, highlighting its potential as biomarker for inflammation and disease activity. TSPAN32 may play a crucial role in shaping adaptive immune responses in RA, opening avenues for novel therapeutic strategies targeting this tetraspanin family member.
本研究旨在探讨四跨膜蛋白 32（TSPAN32）在类风湿关节炎（RA）中的作用。目的是评估 TSPAN32 在实验性 RA 模型和 RA 患者免疫细胞中的表达水平，探索其作为 RA 发病机制中调节因子的潜力。该研究采用大鼠佐剂性关节炎和小鼠胶原诱导性关节炎（CIA）作为实验模型。体外分析包括评估疾病不同阶段免疫细胞中 TSPAN32 的表达。通过分析未经药物治疗和治疗后的 RA 患者的转录组数据集，进行了基于计算机的数据分析，以将 TSPAN32 的表达与临床参数相关联。在 CIA 小鼠的脾细胞中进行 TSPAN32 过表达实验，旨在证明其对抗原特异性免疫反应的功能影响。动物模型显示 TSPAN32 显著下调，特别是在滑膜浸润 T 细胞中。此外，TSPAN32 过表达抑制了脾细胞中促炎细胞因子的产生。在 RA 患者中，循环和滑膜浸润 T 细胞以及 CD8+T 细胞、B 细胞和 NK 细胞中 TSPAN32 持续下调。药物治疗并未显著改变 TSPAN32 水平。在 RA 患者中，TSPAN32 表达与炎症标志物（CRP、ESR）和临床评分（SDAI）之间观察到负相关。本研究表明，TSPAN32 表达降低是 RA 致病性 T 细胞群的特征，提示其作为炎症和疾病活动的生物标志物的潜力。TSPAN32 可能在塑造 RA 中的适应性免疫反应中发挥关键作用，为靶向该四跨膜蛋白家族成员的新型治疗策略开辟了途径。
