CD226/TIGIT失衡在原发性干燥综合征发病机制中对活化外周双阴性T细胞的作用
The role of imbalanced CD226/TIGIT on activated peripheral double-negative T cells in the pathogenesis of primary Sjögren's syndrome.
作者信息
Deng Chuiwen, Wang Anqi, Li Wenli, Chen Yingying, Li Rongli, Zhao Lidan, Zhou Jiaxin, Zhang Wen, Li Mengtao, Zhao Yan, Zeng Xiaofeng, Fei Yunyun
机构信息
Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.
Department of Rheumatology, Key Myositis Laboratories, China-Japan Friendship Hospital, Beijing, China.
出版信息
Clin Exp Rheumatol. 2024 Dec;42(12):2369-2377. doi: 10.55563/clinexprheumatol/yb63g0. Epub 2024 Sep 10.
OBJECTIVES
To explore whether the balance of CD226 and TIGIT is disturbed in CD3+CD56-TCRαβ+CD4-CD8- (DN) T cells and have a better understanding of the potential role of DN T cells in the pathogenesis of primary Sjögren's syndrome (pSS).
METHODS
The percentage of DN T cells as well as the expression of CD226 and TIGIT was identified by flowmetry. After in vitro stimulation, we further detected the expression of activation and cytotoxic marker, as well as intracellular cytokines secreted by DN T cells.
RESULTS
DN T cells were found to expand in the peripheral blood of pSS patients (1.77±0.66%) and correlate with IgG (r=0.451, p<0.05), C3 (r=-0.438, p<0.05) and C4 (r=-0.470, p<0.05). Imbalanced CD226/TIGIT was observed on peripheral DN T cells of pSS patients, especially the overexpression of inhibitory immunoreceptor TIGIT. The expression ratio of TIGIT and CD226 on DN T cells was elevated in pSS patients and correlated with ESSDAI scores≥5 (r=0.743, p<0.05). Besides, these DN T cells were found to be activated and show strong cytotoxicity.
CONCLUSIONS
The balance between CD226 and TIGIT on DN T cells was disturbed and correlated with the disease activity in pSS patients, which may be implicated in the pathogenesis of pSS.
目的
探讨CD3⁺CD56⁻TCRαβ⁺CD4⁻CD8⁻（双阴性，DN）T细胞中CD226和TIGIT的平衡是否受到干扰，并更好地了解DN T细胞在原发性干燥综合征（pSS）发病机制中的潜在作用。
方法
采用流式细胞术鉴定DN T细胞的百分比以及CD226和TIGIT的表达。体外刺激后，我们进一步检测了激活和细胞毒性标志物的表达，以及DN T细胞分泌的细胞内细胞因子。
结果
发现pSS患者外周血中DN T细胞扩增（1.77±0.66%），且与IgG（r=0.451，p<0.05）、C3（r=-0.438，p<0.05）和C4（r=-0.470，p<0.05）相关。在pSS患者外周DN T细胞上观察到CD226/TIGIT失衡，尤其是抑制性免疫受体TIGIT的过表达。pSS患者DN T细胞上TIGIT与CD226的表达比值升高，且与ESSDAI评分≥5相关（r=0.743，p<0.05）。此外，发现这些DN T细胞被激活并表现出强烈的细胞毒性。
结论
DN T细胞上CD226和TIGIT之间的平衡受到干扰，且与pSS患者的疾病活动相关，这可能与pSS的发病机制有关。
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