Abstract
BackgroundIL-22 and IL-17A are implicated in the pathogenesis of autoimmune diseases. However, the role of IL-22+ and IL-17A+ CD4+ T cells in the pathogenesis of Hashimoto’s thyroiditis (HT) is not fully understood. This study investigates serum IL-22 and IL-17A levels and determines the frequency of circulating IL-22+ CD4+ T cells in HT patients to understand their roles in the pathogenesis of HT.MethodsThe levels of serum IL-22, IL-17A and IFN-γ and the frequency of circulating IL-22+CD4+ and IL-17A+CD4+ T cells in 17 HT patients and 17 healthy controls (HC) were determined by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The levels of serum free triiodothyronine (FT4), free thyroxine (FT3), thyroid stimulating hormone (TSH), anti-thyroid peroxidase (TPO) and anti-thyroglobulin antibodies (TgAb) by chemiluminescent enzyme immunoassay and radioimmunoassay.ResultsThe percentages of circulating IL-22+CD4+ and IL-17+CD4+ T cells (p<0.0001, p<0.0001) and the levels of serum IL-22, IL-17A and IFN-γ (p<0.0001, p<0.0001, p = 0.0210) in the HT patients were significantly higher than that in the HC. The percentages of IL-22+CD4+ T cells were positively correlated with Th17 cells (r = 0.8815, p<0.0001) and IL-17A+IL-22+CD4+ T cells (r = 0.8914, p<0.0001), but were negatively correlated with Th1 cells (r = −0.6110, p<0.0092) in the HT patients. The percentages of Th22 cells, Th17 cells and IL-17A+IL-22+CD4+ T cells were negatively correlated with the levels of serum TSH in the HT patients (r = −0.8402, p<0.0001; r = −0.8589, p<0.0001; r = −0.8289 p<0.0001, respectively).ConclusionsA higher frequency of circulating IL-22+CD4+ and IL-17A+CD4+ T cells may be associated with the development of HT in Chinese patients.
Highlights
Hashimoto’s thyroiditis (HT) is an organ-specific autoimmune disease and is characterized by lymphocytic infiltrates within the thyroid glands [1,2]
There was no significant difference in the distribution of age and gender between the HT patients and healthy controls (HC)
The frequency of CD4+, CD4+IFN-c2IL-17A2IL-22+ (Th22), CD4+IFN-c2IL-17A+IL-222 (Th17), CD4+IFN-c2IL17A+IL-22+ (Th17/The frequency of CD4+IFNc–IL17A–IL-22+ (Th22)) and CD4+IFN-c+ (Th1) T cells was characterized by flow cytometry (Fig. 1)
Summary
Hashimoto’s thyroiditis (HT) is an organ-specific autoimmune disease and is characterized by lymphocytic infiltrates within the thyroid glands [1,2]. While previous studies have shown that antigen-specific CD8+ T cell-mediated cytotoxicity and autoantibody-dependent cytotoxicity are crucial in the pathogenesis of HT, they are regulated by different functional CD4+ T cells [5]. Recent studies indicated that HT patients have a higher frequency of circulating Th17 cells and elevated levels of serum IL-17A [3,8]. It is unclear how Th1 and Th17 cells contribute to the early process of HT. This study investigates serum IL-22 and IL-17A levels and determines the frequency of circulating IL-22+ CD4+ T cells in HT patients to understand their roles in the pathogenesis of HT
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