PATHOGENIC ROLE OF TH17 CELLS IN AUTOIMMUNE THYROID DISEASE AND THEIR UNDERLYING MECHANISMS

Elsevier

Available online 8 February 2023, 101743

Best Practice & Research Clinical Endocrinology & MetabolismAuthor links open overlay panel, , ABSTRACT

Autoimmune thyroid disease, encompassing Graves’ disease and Hashimoto’s thyroiditis, has a very complex etiology. Pathogenesis of the disease involves both genetic susceptibility and environmental triggers. Traditionally, imbalance of T helper cell 1 and 2 was thought to result in the immune disorders in Graves’ disease and Hashimoto’s thyroiditis. However, increasing evidence recently revealed the important role of T helper 17 cell and its relative cellular and secretory components in the pathogenesis and progression of autoimmune thyroid disease. This review is aimed to summarize the published studies on the involvement of T helper 17 cell in autoimmune thyroid disease and discuss the underlying regulatory mechanisms, which could possibly serve as the foundation of discovering new therapeutic targets.

Section snippetsINTRODUCTION

Autoimmune thyroid disease (AITD) is composed of two main classifications: Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). AITD results from loss of immune tolerance toward self-antigens, including thyroglobulin (Tg), thyroperoxidase (TPO) and thyrotropin receptor (TSH-R) [1]. Infiltration of auto-reactive lymphocytes in thyroid gland and production of autoantibodies are direct evidences of autoimmune responses of both GD and HT. While lymphocyte infiltration is more severe in HT than

TH17 AND GRAVES’ DISEASE

Recent studies have shown that the percentage of peripheral Th17 cells in total CD4+ T cells [28], [29], [30**], [31] and serum IL-17 level [28], [32**] were found to be significantly higher in GD patients than normal controls. Increased mRNA levels of RORγt, IL-17 and IL-22 were found in peripheral blood mononuclear cells (PBMCs) from patients with GD than those from normal controls [33]. Furthermore, the associations between Th17 cells, IL-17, and the clinical features of GD were also

TH17 AND HASHIMOTO’S THYROIDITIS

Similar to GD, Th17 cells were found to be closely related to the development of HT. Many studies have shown that the proportion of peripheral Th17 cells [29], [38*], [81], [82**], serum IL-17 level [80**], [82**], [83], [84**], and mRNA levels of IL-17 and RORγt in PBMCs [39], [80**], [81], [82**], [83], [84**]) were significantly higher in HT patients compared with healthy controls. Compared with healthy individuals, a stronger expression of IL-17 was detected in thyroid tissues from HT

SUMMARY

The pathogenic role of Th17 cell, its relevant inflammatory mediators and Th17/Treg imbalance in AITD has been revealed in clinical samples from patients, and proven in in vivo and in vitro experiments. Evidence has been provided that Th17 autoimmunity occurs in patients with GD and HT and correlates with some important clinical features, including level of circulating auto-antibodies against thyroid, disease duration, and the severity and intractability of the AITD. The augment of Th17

CONFLICTS OF INTEREST

The authors have no potential conflicts of interest in authorship or publication.

FUNDING STATEMENT

This work was funded by the National Natural Science Foundation of China (81930024, 82071003, 82000879), the National Key R&D Program of China (2018YFC1106100, 2018YFC1106101), the Research Grant of the Shanghai Science and Technology Committee (20DZ2270800, 17DZ2260100, 19410761100, and 19DZ2331400), the Innovative research team of high-level local universities in Shanghai, the Clinical Research Plan of SHDC (SHDC2020CR3051B), the Project of Medical Robots (IMR-NPH202002) From the Clinical

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