The Role Of The IL-23/IL-17Axis In The Pathogenesis Of Graves’ Disease

Objective：This study is to explore the role of IL-23/IL-17axis insubjects with Graves’ disease, while IL-23/IL-17axis plays an important rolein a number of autoimmune diseases, but it’s not clear in Graves’ disease.Methods：33patients with Graves’ disease as a GD group，15patientswith euthyroid GD as eGD group and22healthy volunteers as a nomalcontrol (NC) group whose age-and sex-matched. Serum were obtained fromeach subject and measured for Serum Free triiodothyronine (FT3),Freetetraiodothyronine (FT4), Hypersensitive thyroid-stimulating hormone(μTSH),Thyroid peroxidase antibody (TPOAb) and Thyroglobulinantibody (TgAb). Peripheral blood was collected and peripheral bloodmononuclear cells (PBMCs) were isolated in the both groups, then PBMCswere cultured in the presence or absence of IL-23in vitro. The expression ofRORγt and IL-17mRNA were examined by semi-quantitative RT-PCR, andthe cell supernatant IL-17levels were measured by enzyme-linkedimmunosorbent assay.Results：1. In GD patients, the mean serum FT3and FT4weresignificantly higher than that in controls (P <0.05), while, μTSH was significantly lower. There was no significant differences in the levels of FT3,FT4, μTSH between eGD and NC group. The levels of TPOAb，TgAbwere significantly higher in GD and eGD group than that in NC group (P<0.05).2. The mRNA expression of RORγt, IL-17and cell supernatant IL-17levels were markedly higher in GD and euthyroid GD group as comparedwith the NC group. There were no significant differences between GD andeuthyroid GD group.3. When PBMCs derived from the three groups were cultured in vitrowith or without IL-23, the expression of RORγt in GD group with IL-23dramatically increased as compared with that in GD group without IL-23andin control group with IL-23. RORγt expression of PBMCs from eGD groupcultured with IL-23was increased compared with that cultured withoutIL-23. The mRNA expression and cell supernatant IL-17levels were alsosignificantly higher than that of GD and eGD cultured without IL-23andcontrol group. There was no difference of the expression of RORγt mRNAand IL-17protein levels between GD and eGD group whatever cultured withor without IL-23.Conclusion：1. Th17and IL-17may paly an important role in thepathogenesis of Graves’ disease.2. IL-23/IL-17axis is associated with the pathogenesis of Graves’disease in it activated term. 3. Our studies demonstrated that IL-23/IL-17axis is associated with thepathogenesis of Graves’ disease. This effect is not dependent on thyroidfunction, but may be associated to the immunity.