Department of Cardiothorcic Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China.
Department of Cardiothorcic Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China.
Mol Immunol. 2021 May;133:67-76. doi: 10.1016/j.molimm.2021.02.011. Epub 2021 Feb 23.
An imbalance in Th17 cells and Tregs may be an important cause of the pathogenesis of thymoma with myasthenia gravis (MG). In this study, 30 patients with simple thymoma and 30 patients with thymoma with MG were analyzed. Flow cytometry analysis of Th17 and Tregs in peripheral blood revealed that the percentages of Th17 in thymoma were lower than those in thymoma with MG, while the percentages of Tregs were higher than those in simple thymoma. Serum cytokine ELISA assays showed that IL-6 levels in simple thymoma were lower than those in MG patients. Further, Th17 and Tregs levels were detected by immunohistochemical double staining of thymoma tissue; the number of positive Th17 cells in thymoma with MG was higher than that in simple thymoma, while positive Tregs showed the opposite results. RORγt protein and mRNA expression in thymoma with MG were both higher than those in simple thymoma. FOXP3 protein and mRNA expression in the thymoma with MG group were lower than those in simple thymoma. The results of coculture of thymoma cells and CD4 + T cells showed that thymoma cells could promote the differentiation of Th17 cells and inhibit the Tregs. Overall, Th17 cells and related transcription factors and cytokines in thymoma with MG patients were higher than those in thymoma patients, whereas, Tregs showed the opposite results, the mechanism may be that thymoma can secrete IL6 and IL21. These findings indicated that imbalances in Th17/Tregs may account for the pathogeny of thymoma with MG.
辅助性 T 细胞 17（Th17）细胞与调节性 T 细胞（Tregs）失衡可能是重症肌无力（MG）合并胸腺瘤发病的重要原因。本研究分析了 30 例单纯胸腺瘤患者和 30 例胸腺瘤合并 MG 患者。外周血 Th17 和 Tregs 的流式细胞术分析显示，胸腺瘤患者 Th17 细胞的百分比低于胸腺瘤合并 MG 患者，而 Tregs 的百分比高于单纯胸腺瘤患者。血清细胞因子 ELISA 检测显示，单纯胸腺瘤患者 IL-6 水平低于 MG 患者。此外，通过胸腺瘤组织免疫组化双染检测 Th17 和 Tregs 水平；MG 合并胸腺瘤患者的 Th17 阳性细胞数高于单纯胸腺瘤患者，而 Tregs 则呈现相反的结果。MG 合并胸腺瘤组织中的 RORγt 蛋白和 mRNA 表达均高于单纯胸腺瘤。MG 合并胸腺瘤组 FOXP3 蛋白和 mRNA 表达均低于单纯胸腺瘤组。胸腺瘤细胞与 CD4+T 细胞共培养的结果表明，胸腺瘤细胞可促进 Th17 细胞分化，抑制 Tregs。总体而言，MG 合并胸腺瘤患者的 Th17 细胞及相关转录因子和细胞因子高于胸腺瘤患者，而 Tregs 则呈现相反的结果，其机制可能是胸腺瘤能分泌 IL6 和 IL21。这些发现表明，Th17/Tregs 失衡可能是胸腺瘤合并 MG 的发病机制之一。
