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
Huihong He, Yuancong Jiang, Jie Qiu, Fengqing Shen, Da Qian, Liwei Meng
Abstract
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.