Objectives

Hyperactivity of T lymphocytes might play an important role in the pathogenesis of primary Sjögren's syndrome (pSS). CD226/T cell immunoglobulin and ITIM domain (TIGIT) pathway is a newly identified immune checkpoint involved in the pathogenesis of cancer and rheumatic diseases. However, its role in the pathophysiology of pSS is obscure. Hence, this study aimed to explore the potential role of CD226/TIGIT expression on T cells in the pathogenesis of pSS.

Methods

In patients with pSS, other rheumatic disease controls (DCs), and healthy controls (HCs), the expression of CD226 and TIGIT on T cells along with their activity following stimulation were detected by flow cytometry. The correlations between the expression of CD226 and TIGIT on T cells and clinical data were analyzed.

Results

The frequencies of CD226/TIGIT expressing CD4⁺ and CD8⁺ T cells were significantly higher in patients with pSS than in HCs and DCs. Among them, the TIGIT/CD226 expressing CD4⁺ T cells closely correlated with pSS disease activity: the percentages of CD4⁺CD226⁺ and CD4⁺TIGIT⁺ T cells were significantly higher in the active pSS than the inactive pSS. The proportion of CD4⁺TIGIT⁺ T cells positively correlated with the erythrocyte sedimentation rate. Further in vitro analysis revealed that CD4⁺CD226⁺ T cells exerted superior effector function than the CD226^- counterparts in both pSS and HCs. TIGIT was preferably expressed on activated cells, and the activity of CD4⁺TIGIT⁺ T cells was comparable with CD4⁺TIGIT⁻ T cells in HCs. However, in pSS, CD4⁺TIGIT⁺ T cells showed enhanced activity than the CD4⁺ TIGIT⁻ T cells.

Conclusion

CD226/TIGIT checkpoint molecules were over-expressed on T cells in pSS. Proportional and functional alteration of CD226/TIGIT expressing CD4⁺ T cells may be involved in the pathogenesis of pSS, and be a potential novel therapeutic target for the disease.

中文翻译：

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原发性干燥综合征发病机制中 T 细胞上 CD226/TIGIT 免疫检查点的改变。

目标

T 淋巴细胞的过度活跃可能在原发性干燥综合征 (pSS) 的发病机制中起重要作用。CD226/T 细胞免疫球蛋白和 ITIM 结构域 (TIGIT) 通路是一个新发现的免疫检查点，涉及癌症和风湿病的发病机制。然而，它在 pSS 病理生理学中的作用尚不清楚。因此，本研究旨在探讨 CD226/TIGIT 表达在 T 细胞上在 pSS 发病机制中的潜在作用。

方法

在 pSS 患者、其他风湿性疾病对照 (DC) 和健康对照 (HC) 中，通过流式细胞术检测 T 细胞上 CD226 和 TIGIT 的表达以及它们在刺激后的活性。分析了T细胞上CD226和TIGIT的表达与临床数据的相关性。

结果

在 pSS 患者中，CD226/TIGIT 表达 CD4 ⁺和 CD8 ⁺ T 细胞的频率显着高于 HC 和 DC。其中，表达TIGIT/CD226的CD4 ⁺ T细胞与pSS疾病活动度密切相关：CD4 ⁺ CD226 ⁺和CD4 ⁺ TIGIT ⁺ T细胞在活跃的pSS中所占的百分比明显高于不活跃的pSS。CD4 ⁺ TIGIT ⁺ T细胞比例与血沉呈正相关。进一步的体外分析表明 CD4 ⁺ CD226 ⁺T细胞比CD226施加优良的效应子功能^-在这两个PSS和碳氢化合物对应。TIGIT优选在活化细胞上表达，并且CD4 ⁺ TIGIT ⁺ T细胞的活性与HC中的CD4 ⁺ TIGIT ^- T细胞相当。然而，在 pSS 中，CD4 ⁺ TIGIT ⁺ T 细胞显示出比 CD4 ⁺ TIGIT ^- T 细胞增强的活性。

结论

CD226/TIGIT 检查点分子在 pSS 中的 T 细胞上过度表达。表达 CD226/TIGIT 的 CD4 ⁺ T 细胞的比例和功能改变可能参与 pSS 的发病机制，并成为该疾病的潜在新治疗靶点。