title: The possible role of CD4⁺CD25(high)Foxp3⁺/CD4⁺IL-17A⁺ cell imbalance in the autoimmunity of patients with Hashimoto thyroiditis.
abstract: Hashimoto thyroiditis (HT) is a prototypic organ-specific autoimmune thyroid disease, for which the exact etiology remains unclear. The aim of this study was to investigate dynamic changes in regulatory T cell (Treg) and T helper 17 cell (Th17) populations in patients with HT at different stages of thyroid dysfunction, as well as to analyze the possible correlation between the Treg/Th17 cell axis and autoimmune status in HT. We assessed thyroid function and autoantibody serology both in HT patients and in healthy controls (HCs) and divided HT patients into three subgroups according to thyroid function. We then determined the percentages of Treg and Th17 cells in peripheral blood mononuclear cells and analyzed mRNA expression of the Treg and Th17 cell-defining transcription factors Foxp3 and RORγt. In addition, serum levels of TGF-β and IL-17A were assessed. We found that the percentage of Treg cells, Foxp3 mRNA levels, and the ratio of Treg/Th17 cells were all significantly lower in HT patients, while Th17 cell percentages and RORγt mRNA levels were significantly higher. Interestingly, we also observed significant differences in these measurements between HT patient subgroups. Serum IL-17A levels were markedly increased in HT patients, while serum concentrations of TGF-β were lower, compared to HCs. The ratio of Treg/Th17 cells was negatively correlated with the levels of serum thyroperoxidase antibody, thyroglobulin antibody, and thyrotropin (TSH) in HT patients. Taken together, our data suggest that the balance between Treg and Th17 cells shifts in favor of Th17 cells during clinical progression of HT, which is negatively correlated with levels of thyroid-specific autoantibodies and TSH, implying that Treg/Th17 cell imbalance may contribute to thyroid damage in HT.
authors.affiliation: Department of Endocrinology and Metabolism, Binzhou Medical University Hospital, Binzhou, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Xue
authors.affiliation: International Office, Binzhou Medical University Hospital, Binzhou, China.
authors.forename: Xiurong
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Dermatology, Binzhou Medical University Hospital, No. 661 Second Huanghe Road, Binzhou, 256603, China. doctor_malei@hotmail.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Endocrinology and Metabolism, Binzhou Medical University Hospital, Binzhou, China.
authors.forename: Shoujun
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of Endocrinology and Metabolism, Shanxi Dayi Hospital, Taiyuan, China.
authors.forename: Yuanbin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, Binzhou Medical University Hospital, Binzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism, Binzhou Medical University Hospital, Binzhou, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Endocrinology and Metabolism, Binzhou Medical University Hospital, Binzhou, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D050031:Hashimoto Disease / Q000097:blood / Q000276:immunology*; D006801:Humans; D020381:Interleukin-17 / Q000097:blood*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D058504:Th17 Cells / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000097:blood; D055815:Young Adult
chemical_list: D001323:Autoantibodies; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508717:IL17A protein, human; C508017:IL2RA protein, human; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D016212:Transforming Growth Factor beta
keywords: Autoimmunity; Hashimoto thyroiditis; Regulatory T cell; T helper 17 cell; Thyroid function