Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Division of Endocrinology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
Sci Rep. 2019 Apr 10;9(1):5886. doi: 10.1038/s41598-019-42442-0.
Melatonin (MLT) plays a significant role in both innate and adaptive immunity, and dysregulation of the MLT signature can modify autoimmune disease phenotypes. In this study, the influence of exogenous MLT administration on regulating autoimmune thyroiditis animal models was evaluated. An experimental autoimmune thyroiditis model was established in MLT-synthesizing (CBA) and MLT-deficient (C57BL/6) mice by immunization with human thyroidglobulin (TG), which features thyrotoxicosis, thyrocyte damage, and CD3 T cell infiltration. In TG-immunized CBA mice, exogenous MLT administration in drinking water (6 μg/ml) enhanced thyroiditis and increased TG-specific splenocyte proliferation but not the anti-thyroglobulin antibody (ATA) titer, while MLT alone caused no significant alteration in thyroid function or histopathology. Meanwhile, MLT administration did not modify thyroid function, the ATA titer, or the thyroid histopathology, but results showed an increase in the splenocyte proliferative capacity in TG-immunized C57BL/6 mice. Collectively, our data showed that early exogenous MLT modified the progression of autoimmune thyroiditis through T cell-driven immunity, and excess MLT worsened the clinical and pathological features.
褪黑素 (MLT) 在先天和适应性免疫中都发挥着重要作用，而 MLT 特征的失调可能会改变自身免疫性疾病的表型。在这项研究中，评估了外源性 MLT 给药对调节自身免疫性甲状腺炎动物模型的影响。通过用人甲状腺球蛋白 (TG) 免疫 CBA 和 MLT 缺陷 (C57BL/6) 小鼠建立实验性自身免疫性甲状腺炎模型，其特征是甲状腺毒症、甲状腺细胞损伤和 CD3 T 细胞浸润。在 TG 免疫的 CBA 小鼠中，在饮用水中添加外源性 MLT（6μg/ml）增强了甲状腺炎并增加了 TG 特异性脾细胞增殖，但不增加抗甲状腺球蛋白抗体 (ATA) 滴度，而 MLT 本身对甲状腺功能或组织病理学没有显著改变。同时，MLT 给药并未改变甲状腺功能、ATA 滴度或甲状腺组织病理学，但结果显示 TG 免疫的 C57BL/6 小鼠的脾细胞增殖能力增加。总的来说，我们的数据表明，早期外源性 MLT 通过 T 细胞驱动的免疫改变了自身免疫性甲状腺炎的进展，而过量的 MLT 则加重了临床和病理特征。
