Hu Bo, Luo Yang, Ding Xiangyu, Sun Min, Niu Li
Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
First Clinical Medical College, Anhui Medical University, Hefei, Anhui, China.
Clin Exp Immunol. 2025 Jan 21;219(1). doi: 10.1093/cei/uxaf043.
Myasthenia gravis (MG) is an autoimmune disease commonly associated with immune disorders in thymoma. The role of thymus myoid cells (TMCs) in the pathogenesis of autoimmune diseases has attracted much attention. Therefore, the present study was designed to reveal the impact of TMCs on the pathophysiology of tumor-associated MG (TAMG). This study included clinical patients and healthy volunteers and validated the potential role of TMCs in TAMG progression using a TMCs-deficient mouse model. Correlative findings showed that TMCs deletion affected thymic architecture in MG patients, as evidenced by the expression of key myogenic factors as well as AChR and RyRs receptors in the thymus. Further experimental validation showed that TMCs deletion increased the levels of Th1 and Th17 cells, decreased the levels of Th2 and Treg cells, and altered the secretion of corresponding cytokines, including IL-2, IL-4, IL-17, IL-22, and TGF-β concentrations. Co-culture of CD4+ T cells with Thy0517 cells or CD4+ T cells with a myoblastoid cell line using the Transwell system demonstrated that deletion of TMC inhibited the differentiation of CD4+ T cells to Treg cells. In this study, we hypothesized that TMCs are involved in TAMG progression by regulating CD4+ T cell differentiation.
重症肌无力(MG)是一种自身免疫性疾病,通常与胸腺瘤中的免疫紊乱有关。胸腺肌样细胞(TMCs)在自身免疫性疾病发病机制中的作用备受关注。因此,本研究旨在揭示TMCs对肿瘤相关性MG(TAMG)病理生理学的影响。本研究纳入了临床患者和健康志愿者,并使用TMCs缺陷小鼠模型验证了TMCs在TAMG进展中的潜在作用。相关研究结果表明,TMCs缺失影响了MG患者的胸腺结构,胸腺中关键生肌因子以及乙酰胆碱受体(AChR)和兰尼碱受体(RyRs)的表达证明了这一点。进一步的实验验证表明,TMCs缺失增加了Th1和Th17细胞水平,降低了Th2和调节性T(Treg)细胞水平,并改变了相应细胞因子的分泌,包括白细胞介素-2(IL-2)、白细胞介素-4(IL-4)、白细胞介素-17(IL-17)、白细胞介素-22(IL-22)和转化生长因子-β(TGF-β)的浓度。使用Transwell系统将CD4 + T细胞与Thy0517细胞或CD4 + T细胞与成肌样细胞系共培养表明,TMCs缺失抑制了CD4 + T细胞向Treg细胞的分化。在本研究中,我们假设TMCs通过调节CD4 + T细胞分化参与TAMG进展。