Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Scand J Rheumatol. 2011;40(5):334-40. doi: 10.3109/03009742.2010.547871. Epub 2011 Mar 30.
T-cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) is a novel transmembrane protein that is involved in the regulation of T-helper 1 (Th1)-cell-mediated immunity. This study was undertaken to investigate the expressions of TIM-3 and its ligand galectin 9 (Gal-9) with respect to disease activity in rheumatoid arthritis (RA).
Blood was collected from 39 RA patients and 31 healthy controls. Blood leucocyte TIM-3 and Gal-9 mRNA levels and RA disease activity were determined. Synovial tissue (ST) from five RA patients and five osteoarthritis (OA) patients were examined for TIM-3 mRNA expression and were also analysed for TIM-3 by immunohistology.
TIM-3 mRNA expression was significantly higher in the ST of RA patients than in the ST of OA patients. TIM-3 was expressed in the synovial sublining area in ST of RA patients but not in OA ST. TIM-3 mRNA expression from peripheral blood mononuclear cells (PBMCs) of RA patients was negatively correlated with the 28-joint Disease Activity Score (DAS28). Gal-9 mRNA level in PBMCs of RA patients was higher than in healthy controls, and was significantly higher in patients with low disease activity compared to those with moderate to high disease activity. Gal-9 mRNA expression in PBMCs of RA patients was positively correlated with forkhead box P3 (FoxP3) mRNA expression.
TIM-3 and its interaction with Gal-9 are closely associated with RA disease activity and may play an important role in the pathogenesis of RA. In addition to the negative regulatory effect of Gal-9 mediated through the TIM-3-Gal-9 pathway, Gal-9 may exert its suppressive effect on RA disease activity by modulation of regulatory T (Treg) cells.
T 细胞免疫球蛋白和粘蛋白结构域包含分子 3（TIM-3）是一种新型的跨膜蛋白，参与调节辅助性 T 细胞 1（Th1）-细胞介导的免疫。本研究旨在探讨 TIM-3 及其配体半乳糖凝集素 9（Gal-9）与类风湿关节炎（RA）疾病活动度的关系。
采集 39 例 RA 患者和 31 例健康对照者的血液，检测外周血白细胞 TIM-3 和 Gal-9mRNA 水平及 RA 疾病活动度。取 5 例 RA 患者和 5 例骨关节炎（OA）患者的滑膜组织（ST），检测 TIM-3mRNA 表达情况，并进行 TIM-3 免疫组织化学分析。
RA 患者的 ST 中 TIM-3mRNA 表达明显高于 OA 患者的 ST。RA 患者 ST 中的 TIM-3 表达于滑膜衬里下层，而 OA ST 中则无表达。RA 患者外周血单个核细胞（PBMCs）的 TIM-3mRNA 表达与 28 关节疾病活动度评分（DAS28）呈负相关。RA 患者 PBMCs 中 Gal-9mRNA 水平高于健康对照组，且低疾病活动度患者高于中至高度疾病活动度患者。RA 患者 PBMCs 中 Gal-9mRNA 表达与叉头框 P3（FoxP3）mRNA 表达呈正相关。
TIM-3 及其与 Gal-9 的相互作用与 RA 疾病活动密切相关，可能在 RA 的发病机制中发挥重要作用。除了 Gal-9 通过 TIM-3-Gal-9 途径介导的负调控作用外，Gal-9 可能通过调节调节性 T（Treg）细胞对 RA 疾病活动度发挥其抑制作用。
