Expression of human T cell immunoglobulin domain and mucin-3 (TIM-3) and TIM-3 ligands in peripheral blood from patients with systemic lupus erythematosus
Expression of human T cell immunoglobulin domain and mucin-3 (TIM-3) and TIM-3 ligands in peripheral blood from patients with systemic lupus erythematosus
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系统性红斑狼疮患者外周血中人T细胞免疫球蛋白结构域和粘蛋白3（TIM-3）和TIM-3配体的表达
DOI：
10.1007/s00403-016-1665-4
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发表时间：
2016-10-01
影响因子：
3
通讯作者：
Liu, Cuiping
中科院分区：
文献类型：
--
作者：
Jiao, Qingqing;Qian, Qihong;Liu, Cuiping
系统性红斑狼疮（SLE）是一种典型的系统性自身免疫性疾病。T细胞免疫球蛋白和粘蛋白结构域（TIM）家族与自身免疫性疾病有关，但其在SLE患者免疫细胞中的表达水平仍不确定。本研究的目的是研究TIM-3和Galectin-9 （Gal-9）是否参与SLE的发病机制。共招募30例SLE患者和30例健康对照者，通过流式细胞术检测其外周血单个核细胞（PBMCs）中TIM-3的表达水平。同时，分别采用酶联免疫吸附测定（ELISA）试剂盒和免疫荧光染色法检测血清和PBMCs中Gal-9的表达水平。研究了TIM-3或Gal-9表达水平与SLE疾病活动指数（SLEDAI）的关系。最后，探讨了TIM-3和Gal-9通路在SLE发病机制中的作用。结果显示，SLE患者CD4+T细胞、CD8+T细胞、CD56+T细胞及血清中TIM-3和Gal-9的表达水平明显高于健康对照组。我们发现SLE患者血清和pmbc中Gal-9的表达水平明显高于健康对照组。SLE患者TIM-3和Gal-9表达上调与SLEDAI评分密切相关。此外，在SLE患者中，Gal-9阻断抗体显著抑制cd3刺激的PBMC增殖和th1来源的细胞因子（IL-2、IFN-γ和TNF-α）、th2来源的细胞因子（IL-4、IL-10）、th17来源的细胞因子（IL-17A）以及促炎因子（IL-6）的释放。结果表明，TIM-3和Gal-9的表达增加可能是SLE诊断的生物标志物，TIM-3途径可能是SLE治疗的靶点。
Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease. The T cell immunoglobulin and mucin domain (TIM) family is associated with autoimmune diseases, but its level of expression in the immune cells of patients with SLE is still uncertain. The aim of this study was to examine whether TIM-3 and Galectin-9 (Gal-9) contribute to the pathogenesis of SLE. In total, 30 patients with SLE and 30 healthy controls were recruited, and their levels of TIM-3 expression in peripheral blood mononuclear cells (PBMCs) were examined via flow cytometry. Meanwhile, the levels of Gal-9 expression in serum and in PBMCs were measured via an enzyme-linked immunosorbent assay (ELISA) kit and immunofluorescence staining, respectively. The relation between the level of TIM-3 or Gal-9 expression and the SLE disease activity index (SLEDAI) was also studied. Finally, the function of the TIM-3 and Gal-9 pathway in the pathogenesis of SLE was explored. Our results showed that the levels of expression of TIM-3 and Gal-9 on CD4+T cells, CD8+T cells, CD56+T cells and in serum in patients with SLE were significantly higher than those of healthy controls. We found that the level of Gal-9 expression was significantly higher in both serum and PMBCs of patients with SLE than in healthy controls. The up-regulation of TIM-3 and Gal-9 expression in patients with SLE was closely related to the SLEDAI scores. In addition, Gal-9 blocking antibody significantly inhibited CD3-stimulated PBMC proliferation and Th1-derived cytokines (IL-2, IFN-γ, and TNF-α), Th2-derived cytokines (IL-4, IL-10), a Th17-derived cytokine (IL-17A), and release of a pro-inflammatory factor (IL-6) in patients with SLE. The results suggest that increased expression of TIM-3 and Gal-9 may be a biomarker for SLE diagnosis and that the TIM-3 pathway may be a target for SLE treatment.