The diverse immunoregulatory role of iodine in thyropathy.

BACKGROUND

Iodine is an environmental factor that contributes to the development of autoimmune thyroid diseases (AITDs).

OBJECTIVE

In this study, we evaluated the influence of excessive iodine in initiating and modulating AITD in different mouse models.

METHODS

We administered exogenous iodide in drinking water (0.15% sodium iodide) to naïve C57BL/6J(B6) mice, human thyroglobulin (hTg)-immunized B6 mice, and a spontaneous autoimmune thyroiditis (NOD.H-2h4) model. We then measured plasma thyroxine (T4) and anti-thyroglobulin antibody (ATA) and gathered microarray data from the Gene Expression Omnibus (GSE16957-GSM424738) for a gene set enrichment analysis (GSEA), ensuring the robustness and validity of our findings.

RESULTS

In the hTg-induced thyroiditis model, iodide administration reduced plasma T4 and ATA levels and suppressed hTg-specific splenocytes. In contrast, despite no significant changes in T4 levels, prominent thyroid inflammation and increased CD3+ and F4/80+ cell infiltration were detected in the iodide administration alone group. On the other hand, after iodide treatment, plasma T4 was reduced but without a significant anti-thyroid extract antibody titer or pathological changes in the NOD.H-2h4 mice. The GSEA showed that human thyrocyte culture incubated with iodide treatment provoked immunologic and inflammatory pathways, including tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, interferon (IFN)-γ, inflammatory responses. Additionally, cell damage (hypoxia-related), immune cell-attracting, and migration-related signatures were also excited.

CONCLUSIONS

We demonstrated the influence of iodine in initiating thyroid inflammation in naïve mice and human thyrocytes, and modulating the thyroid function in hTg-immunized thyroiditis and NOD.H-2h4 models. Further studies to dissect the actual mechanism are still required.