Abstract
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.
Highlights
Melatonin (MLT) plays a significant role in both innate and adaptive immunity, and dysregulation of the MLT signature can modify autoimmune disease phenotypes
We created a mouse thyroiditis model by repeated TG injections in different mouse strains, which manifested as thyrotoxicosis, thyroid follicle destruction, and CD3+ T cell infiltration
We showed that exogenous MLT administration enhanced TG-induced thyroiditis in both the initial and recovery phases in CBA mice
Summary
Melatonin (MLT) plays a significant role in both innate and adaptive immunity, and dysregulation of the MLT signature can modify autoimmune disease phenotypes. 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. 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. Evidence demonstrated that MLT, together with its key synthesizing enzymes, and the MT1 receptor protein exist in the thyroid gland, which further implied that the MLT signature could exert certain biological activities in thyrocytes[18]. In our published genetic association study, we found that the single-nucleotide polymorphism of MTNR1A, coding the MT1 protein, was associated with a susceptibility to GD and thyroid autoantibody formation, which supports the notion that the MLT signature can influence the occurrence of AITD and clinical features[20]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
