Dietary iron supplementation modulates thyroid immune homeostasis and ameliorates experimental autoimmune thyroiditis in mice

Abstract

Background: Autoimmune thyroiditis (AITD) is a prevalent autoimmune disorder, and epidemiological evidence suggests that dietary iron intake is inversely associated with AITD risk. However, the functional role of dietary iron in modulating thyroid autoimmunity remains poorly understood. Objective: This study aimed to investigate the effects of dietary iron interventions on thyroid autoimmune responses and to explore the potential of iron supplementation as a nutritional strategy for AITD prevention. Methods: Female non-obese diabetic mice carrying the H-2^h4 haplotype (NOD.H-2^h4) mice were fed iron-deficient (ID), normal-iron (ND), or iron-supplemented (IS) diets, and EAT was induced using high-iodine drinking water. Serum levels of thyroid autoantibodies, hormones, and cytokines were measured by ELISA. Histopathological changes and the expression profiles of T/B cell subsets (Th1, Th2, Th17, Treg, Tfh, and B10) in thyroid tissues were assessed using hematoxylin–eosin staining and immunofluorescence. Results: Compared to the EAT + ND group, mice in the iron-supplemented group (EAT + IS) exhibited attenuated thyroidal lymphocyte infiltration, decreased levels of TPO-Ab, Tg-Ab, TSH, and proinflammatory cytokines (IFN-γ, IL-17, IL-21, and BAFF), along with increased expression of anti-inflammatory cytokines (IL-10 and TGF-β). Moreover, Treg and B10 cell populations were significantly upregulated, whereas Th1, Th17, and Tfh cells were decreased. The iron-deficient group (EAT + ID) also showed a reduction in inflammatory parameters; however, this effect was likely driven by nonspecific immunosuppression rather than enhanced regulatory immunity. Conclusion: Our findings demonstrate that dietary iron supplementation promotes regulatory immune responses and attenuates autoimmune thyroiditis, highlighting the functional significance of adequate dietary iron intake in maintaining thyroid immune homeostasis. These results provide experimental support for dietary iron optimization as a potential nutritional approach for AITD prevention.