The increased but non-predominant expression of Th17- and Th1-specific cytokines in Hashimoto’s thyroiditis but not in Graves’ disease

Qiu Qin,Ping Liu,Ni Yan,Lin Liu,Rong Wang,Jin-An Zhang,Madhu Pandey,Jing Yang,Xuan Wang

doi:10.1590/s0100-879x2012007500168

Abstract

Hashimoto's thyroiditis (HT) is considered to be mediated mainly by Th1 cells, but it is not known whether Graves' disease (GD) is associated with Th1 or Th2 predominance. Th17 cells, a novel subset of Th cells, play a crucial role in the pathogenesis of various autoimmune disorders. In the present study, the expression of IL-17A and IFN-γ was investigated in patients with HT or GD. mRNA expression of IL-17A and IFN-γ in peripheral blood mononuclear cells (PBMC) from 43 patients with autoimmune thyroid disease (AITD) and in thyroid tissues from 40 AITD patients were measured by real-time quantitative PCR. The protein expression of IL-17A and IL-23p19 was examined by immunohistochemistry in thyroid tissues from 28 AITD patients. The mRNA levels of IL-17A and IFN-γ were higher in both PBMC and thyroid tissues of HT patients than in controls (mRNA levels are reported as the cytokine/β-actin ratio: IL-17 = 13.58- and 2.88-fold change and IFN-γ = 16.54- and 2.74-fold change, respectively, P < 0.05). Also, the mRNA levels of IL-17A and IFN-γ did not differ significantly in GD patients (P > 0.05). The high protein expression of IL-17A (IOD = 15.17 ± 4.8) and IL-23p19 (IOD = 16.84 ± 7.87) in HT was confirmed by immunohistochemistry (P < 0.05). The similar high levels of IL-17A and IFN-γ suggest a mixed response of Th17 and Th1 in HT, where both cells may play important roles in the destruction procedure by cell-mediated cytotoxicity.

Highlights

Autoimmune thyroid diseases (AITD), characterized by autoantibody production and lymphocyte infiltration that usually result in tissue inflammation and cell destruction, mainly comprise Graves’ disease (GD) and Hashimoto’s thyroiditis (HT)
IL-17A and IFN-γ mRNA levels were higher in the peripheral blood of patients with HT compared to healthy controls (P < 0.05; Figures 1A and 2)
IL-17A and IFN-γ mRNA levels were significantly higher in thyroid tissues from patients with HT than from healthy controls (P < 0.01)

Summary

Introduction

Autoimmune thyroid diseases (AITD), characterized by autoantibody production and lymphocyte infiltration that usually result in tissue inflammation and cell destruction, mainly comprise Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). Most studies have found a significantly higher expression of interferon-gamma (IFN-γ) (a typical type I cytokine) in HT, suggesting that the cytokine profile in HT has a Th1 bias [2,3,4] This finding is consistent with other autoimmune inflammatory diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS). Animal models of collagen-induced arthritis and experimental autoimmune encephalomyelitis have shown that knockout of the IFN-γ gene or the absence of IFN-γ signal/receptors in vivo does not provide protection from autoimmune diseases, but rather promotes it [5] These conflicting results strongly suggest the possibility of the participation of another T-cell subset in the development of these autoimmune diseases

Methods

Results

Conclusion