Role of interleukin 17 and T helper cells 17 cells as a new immune target and signalling in the pathogenesis and treatment of autoimmune thyroid diseases.

OBJECTIVE

This study aims to systematically review the molecular and cellular mechanisms by which the interleukin 17 (IL-17)/T helper cells (Th17) signalling axis contributes to Graves' disease (GD) and Hashimoto's thyroiditis (HT), with particular focus on IL-17/Th17/T regulatory cells (Treg) balance, and to summarize the development of IL-17-targeted therapies for autoimmune thyroid disease (AITD).

METHODS

A comprehensive literature review (up to 2025) was conducted, encompassing human studies, animal models, and pre-clinical investigations related to IL-17/Th17 biology in AITD.

RESULTS

IL-17 levels are elevated in both untreated and intractable GD. IL-17/IL-17RA signalling enhances the expression of IL-6, chemokine CXC ligand 10, and intercellular cell adhesion molecule-1, thereby amplifying thyroid inflammation. The IL-23/IL-17 axis and Th17/Treg imbalance are strongly associated with thyroid-associated ophthalmopathy. Serum and tissue IL-17 concentrations correlate positively with TPOAb or TgAb titres and early fibrosis, while Th17 predominance precedes Th1-mediated tissue destruction. Excessive iodine intake further drives naïve Tregs toward Th17 differentiation. Shared TGF-β signalling drives the reciprocal development of Th17 and Treg cells, with retinoid-related orphan receptor gamma t and Forkhead box protein P3 acting as molecular switches. Disruption of this balance contributes to the progression of AITD. Several pre-clinical agents (JiaYanKangTai, Yanghe decoction, LY294002) have been found to ameliorate experimental autoimmune thyroiditis by inhibiting IL-17 signalling or restoring Th17/Treg equilibrium; however, clinical translation remains limited.

CONCLUSIONS

IL-23/IL-17 axis and Th17/Treg imbalance are critical checkpoints in the AITD pathogenesis. IL-17 represents a promising, yet still experimental immunotherapeutic target, warranting rigorous clinical investigation.