Ding Haoran, Qin Jiabo, Liu Zhijian, Shi Xianbiao, Guan Wenxian, Sang Jianfeng
Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China; Division of Thyroid Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China.
Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China.
Tissue Cell. 2024 Dec;91:102596. doi: 10.1016/j.tice.2024.102596. Epub 2024 Oct 25.
Hashimoto's thyroiditis is a chronic autoimmune inflammatory disease with a high prevalence and currently lacks effective treatment options. Previous preclinical and clinical trials have established mesenchymal stem cells (MSCs) as a promising therapeutic approach; however, there is limited research on MSC treatment for Hashimoto's thyroiditis, and the underlying molecular mechanisms remain unclear.
MSCs isolated from 4 to 6-week-old Lewis rats were employed for thyroiditis treatment. The efficacy of MSCs was assessed through histological and serological parameters. Molecular mechanisms of MSC therapy for Hashimoto's thyroiditis were explored by examining macrophage presence within thyroid tissue and relevant pathways.
In this study, we observed elevated oxidative stress and endoplasmic reticulum stress within the thyroid tissue of Hashimoto's thyroiditis patients, and MSC therapy effectively mitigated this process. Furthermore, we found that the therapeutic potential of MSCs in the EAT model depended on the STING pathway. MSCs reduced endoplasmic reticulum stress and inflammasome levels within the thyroid tissue by modulating the STING pathway. Additionally, MSCs inhibited the expression of IRE1α in thyroid tissue macrophages, thereby reducing the polarization of M1-type macrophages CONCLUSIONS: The STING pathway appears to be a crucial mechanism by which MSCs modulate macrophage polarization in thyroid tissue, offering a potential treatment for thyroiditis.
桥本甲状腺炎是一种患病率较高的慢性自身免疫性炎症性疾病，目前缺乏有效的治疗方法。先前的临床前和临床试验已将间充质干细胞（MSCs）确立为一种有前景的治疗方法；然而，关于MSCs治疗桥本甲状腺炎的研究有限，其潜在的分子机制仍不清楚。
使用从4至6周龄Lewis大鼠分离的MSCs进行甲状腺炎治疗。通过组织学和血清学参数评估MSCs的疗效。通过检查甲状腺组织内巨噬细胞的存在情况和相关途径，探索MSCs治疗桥本甲状腺炎的分子机制。
在本研究中，我们观察到桥本甲状腺炎患者甲状腺组织内氧化应激和内质网应激升高，而MSCs治疗有效地减轻了这一过程。此外，我们发现MSCs在实验性自身免疫性甲状腺炎（EAT）模型中的治疗潜力取决于干扰素基因刺激蛋白（STING）途径。MSCs通过调节STING途径降低甲状腺组织内的内质网应激和炎性小体水平。此外，MSCs抑制甲状腺组织巨噬细胞中肌醇需求酶1α（IRE1α）的表达，从而减少M1型巨噬细胞的极化。结论：STING途径似乎是MSCs调节甲状腺组织中巨噬细胞极化的关键机制，为甲状腺炎提供了一种潜在的治疗方法。
