Immuno-regulatory effects of hydroxychloroquine in experimental autoimmune thyroiditis

Hydroxychloroquine (HCQ) is a commonly used immunomodulatory drug in various autoimmune diseases; however, its role in autoimmune thyroid diseases (AITDs) remains unclear.

This study aimed to evaluate the potential effects of HCQ in autoimmune thyroiditis using both naïve and experimental autoimmune thyroiditis (EAT) mouse models.

Mice were administered HCQ via drinking water. Plasma levels of free thyroxine (FT4), anti-thyroglobulin antibody (ATA), B-cell activating factor (BAFF), and interferon-α (IFN-α), along with thyroid histopathology, were assessed. Thyroid tissues were subjected to next-generation sequencing (NGS), followed by over-representation analysis (ORA) and gene set enrichment analysis (GSEA) for functional enrichment evaluation.

In EAT mice, HCQ treatment did not significantly affect FT4 or ATA levels, nor did it alter thyroid histological features. However, HCQ reduced human thyroglobulin stimulated splenocyte metabolic activity and plasma BAFF levels, indicating a systemic immunomodulatory effect. NGS of thyroid tissues revealed widespread upregulation of immune and inflammatory genes in EAT mice, which were partially attenuated by HCQ. GSEA also confirmed downregulation of immune-related pathways, including IL-6-JAK-STAT3 signaling and allograft rejection. No significant changes were observed in naïve mice treated with HCQ.

In the context of autoimmune thyroiditis, HCQ showed preliminary immunomodulatory effects on certain immunological markers without recovering histological damage in the short term. Further long-term and mechanistic studies are warranted to clarify HCQ's therapeutic potential in autoimmune thyroiditis.