Effect Of Imbalance Between Th17Cells And Treg Cells In The Pathogenesis Of Children With Henoch-schonlein Purpura

Objective：The purpose of this study was to explore theaffects of Th17cell and its transcription factor RORγt, Treg cell and itstranscription factor FoxP3in the pathogenesis of Henoch-Schonleinpurpura of children, to elucidate the pathogenesis of Henoch-Schonleinpurpura from the imbalance of Th17and Treg cell and its regulatingmolecular mechanism, to investigate the changes of serum IL-17A,TGF-β1, IL-6and IL-2of Henoch-Schonlein purpura in acute stage andtheir adjusting function to the balance of Th17and Treg cells. The studymay offer a new strategy for the treating of children’s Henoch-Schonleinpurpura from the regulating the balance of Th17and Treg cells.Methods：Forty children with Henoch-Schonlein purpura in acute stageadmitted in our hospital from February2012and March2013wereenrolled in this study. Forty healthy children were simultaneously takenas control. The expression of RORγt mRNA and FoxP3mRNA inperipheral mononuclear cells was detected by Real Time PCR usingSYBR Green I. The levels of IL-17A,TGF-β1,IL-2and IL-6in serumwere measured by ABC-ELISA. The ratio of Th17cells and Treg cellswas detected by flow cytometry on peripheral blood mononuclear cells.Results：The results showed that the relative level of RORγt mRNA ofHSP group (1.11±0.51) was significantly higher than those of control group (0.65±0.24)(P<0.01), but the relative level of FoxP3mRNA of theHSP (1.15±0.45) was lower than those of the control (2.32±1.13)(P<0.01). The levels of serum IL-17A, IL-6, TGF-β1of the HSP(40.40±11.81pg/ml,75.38±27.19pg/ml,309.41±81.03pg/ml relatively)was significantly higher than those of the control (20.32±10.70pg/ml,25.16±8.31pg/ml,236.34±66.01pg/ml respectively)(P<0.01, P<0.01,P<0.01), but the level of serum IL-2of the HSP (25.60±13.19pg/ml) waslower than those of the control (34.42±11.69pg/ml)(P<0.01). Theexpression level of Th17cells in the HSP (2.75±0.60%) was significantlyhigher than those of the control (1.41±0.29%)(P<0.01), but the expressionlevel of Treg cells in the HSP (4.56±1.26%) was significantly lower thanthose of the control (7.85±1.97%)(P<0.01). We further demonstrated that,in the children with acute Henoch-Schonlein purpura, a positivecorrelation was found between the Th17cells and RORγt mRNA, IL-17A,IL-6, the correlation coefficient was0.887(P<0.01),0.938（P<0.01) and0.934(P<0.01) respectively. The positive correlation also was showedbetween the expression levels of Treg cells and FoxP3mRNA, IL-2, thecorrelation coefficient was0.834(P<0.01) and0.932(P<0.01)respectively. Conclusion： There were higher expression levels ofTh17cells, RORγt mRNA and IL-17A, and lower expression levels ofTreg cells, FoxP3mRNA of children with HSP in acute phase, whichshowed that Th17/Treg imbalance existed in children with HSP in acute phase. So we can inference that both the strong inflammatory reaction ofTh17cells and the damaged immunosuppressive effect of Treg cells wereinvolved in the pathogenesis of children with HSP, which may be one ofthe important factors of the immune imbalance of children with HSP. Thisstudy clarified one of regulating molecular mechanisms for imbalance ofTh17/Treg. There were increased levels of serum IL-6, TGF-β1and adecreased serum IL-2in children with acute phase of HSP.Simultaneously, in the same group, we found positive correlationsbetween the Th17cells and IL-6, the Treg cells and IL-2. That pointed outthat IL-6, IL-2, TGF-β1might be involved in the pathogenesis of childrenwith HSP, and the changes of IL-6, IL-2, TGF-β1in cytokinemicroenvironment might be involved in regulating imbalance betweenTh17cells and Treg cells. This study provided new thinking and newstrategy for the treatment of HSP from regulating the imbalance betweenTh17cells and Treg cells.