IL-21Up-regulation IL-17in Patients With Graves Disease

Objective: IL-21plays an important role in various autoimmunediseases, but it’s not clear in Graves disease（GD）. The aim of this studywas to examine the plasma levels of Interleukin-17(IL-17), IL-17mRNAand Retinoid-related orphan receptor gammat (RORγt) mRNA in GDgroup, euthyroid GD (eGD) group and control group. Then to examinethe expression of IL-17and RORγt mRNA, IL-17protein levels withIL-21in three groups. Explore the role of the IL-21in subjects withGraves disease.Methods：30patients with Graves disease as GD group,17patientswith euthyroid GD as eGD group and18healthy donors as control group.Electrochemical iumineacence detection was used to determine levels ofthyroid function indexes(FT3, FT4, uTSH) and autoantibodies (TgAb,TPOAb, TRAb). The Peripheral blood mononuclear cells (PBMCs) werecultured in the presence or absence of IL-21in vitro. The levels of IL-17protein were measured by enzyme-linked immunosorbent assay (ELISA).And the expression of IL-17and RORγt mRNA were examined bySemi-quantitative RT-PCR.Results: The level of thyroid function in GD group compared with the control group and eGD group, the differences were statisticallysignificant (P <0.05). But when the control group compared with eGDgroup, the differences were not statistically significant(P>0.05). The levelof thyroid autoantibodies in GD group and eGD group markedly increasedcompared to the control group(P <0.05). But when the GD groupcompared with eGD group, the differences were not statisticallysignificant(P>0.05). The expression of IL-17, RORγt mRNA and IL-17protein levels were markedly higher in GD and euthyroid GD groupcompared to the control group(P <0.05). When PBMCs from the threegroups were cultured in vitro with or without IL-21, the expression ofIL-17, RORγt mRNA, IL-17protein levels in GD group and eGDgroup with IL-21markedly increased compared to that in GD group andeGD group without IL-21and in control group with IL-21(P <0.05). Therewas no difference of the expression of IL-17mRNA, RORγt mRNA andIL-17protein levels between GD and eGD group cultured with or withoutIL-21(P>0.05).Conclusions：The expression of IL-17, RORγt mRNA and IL-17protein levels were markedly higher in GD and euthyroid GD groupcompared to the control group. It is indicated that IL-17plays apathogenic role in autoimmune disease. The expression of IL-17, RORγtmRNA, IL-17protein levels in GD group and eGD group with IL-21markedly increased compared to that in GD group and eGD group without IL-21and in control group with IL-21. These studies indicate that IL-21upregulation IL-17involved in the pathogenesis of Graves disease. Thiseffect may be not based on thyroid function, but may be related to theimmunity.