The role of the IL-23/IL-17 axis in the pathogenesis of Graves’ disease

Abstract

This study is to explore the role of IL-23/IL-17 axis in subjects with Graves’ disease, while IL-23/IL-17 axis plays an important role in a number of autoimmune diseases, but it’s not clear in Graves’ disease. Thirty-three patients with Graves’ disease as a GD group, 15 patients with euthyroid GD as eGD group and 22 healthy volunteers as a control group whose age- and sex-matched. Peripheral blood was collected and peripheral blood mononuclear cells (PBMCs) were isolated in the both groups, then PBMCs were cultured in the presence or absence of IL-23 in vitro. The expression of retinoid-related orphan receptor gamma t (RORγt) and IL-17 mRNA were examined by Semi-quantitative RT-PCR, and the levels of IL-17 protein were measured by enzyme-linked immunosorbent assay. The expression of RORγt, IL-17 mRNA and IL-17 protein levels were markedly higher in GD and euthyroid GD group as compared with the control group. IL-17 levels were still higher in euthyroid GD patients. When PBMCs derived from the three groups were cultured in vitro with or without IL-23, the expression of RORγt in GD group with IL-23 dramatically increased as compared with that in GD group without IL-23 and in control group with IL-23. RORγt expression of PBMCs from eGD group cultured with IL-23 was increased compared with that cultured without IL-23. The levels of IL-17 mRNA and the protein were also significantly higher than that of GD and eGD cultured without IL-23 and control group. There was no difference of the expression of RORγt mRNA and IL-17 protein levels between GD and eGD group cultured with or without IL-23. Our studies demonstrated that IL-23/IL-17 axis is associated with the pathogenesis of Graves’ disease in it activated term. This effect is not dependent on thyroid function, but may be associated to the immunity.