| Objective:This study was to explore the effect of Thl7/Treg cells imbalances on the pathogenesis of Henoch-Schonlein purpura(HSP) in children,to explore how the signal transduction pathways of IL-6/STAT3,IL-2/STAT5 effect the balance of Th17/Treg cells,to explore the changes of serum IL-17A, IL-6, TGF-β1, IL-2 in the acute phase of HSP and its possible mechanisms involved in the pathogenesis of Thl7/Treg cells imbalances.The study was also conducted to provide the experimental basis to clarify the molecular mechanism of Th17/Treg cells imbalances.Methods:Fifty children with Henoch-Schonlein purpura in acute stage admitted in our hospital from March 2013 to April 2014 were enrolled in this study. Fifty healthy children were simultaneously taken as control. The ratio of Th17 cells and Treg cells was detected by flow cytometry on peripheral blood T lymphocytes.The expression of STAT3mRNA and STAT5 mRNA in peripheral mononuclear cells was detected by Real Time PCR using SYBR Green I. The levels of IL-17A,TGF-β1,IL-2 and IL-6 in serum were measured by ABC-ELISA. Results The level of Th17 cells in HSP group was (3.34±0.60%), which was higher than the,control group (0.90±0.28%) (P<0.01), while the level of Treg cells (4.21±1.25) was lower than the control group (6.90±1.23) (P<0.01).The relative expression level of STAT3mRNA of HSP group was 1.92±0.61, which was significantly higher than that of the control group (1.28± 0.63)(P<0.01), while the expression level of STAT5mRNA in HSP group(1.23±0.64) was significantly lower than the control group (1.90±0.56)(P<0.01). Meanwhile, The levels of serum IL-17A, IL-6, TGF-β1 of the HSP group (45.09±12.99pg/ml,83.75±29.91pg/ml, 321.55±81.05pg/ml relatively) were significantly higher than those of the control group(21.80±11.76pg/ml,37.30±12.86pg/ml,239.84±66.04 pg/ml respectively) (P<0.01, P<0.01, P<0.01), but the level of serum IL-2 (27.61±14.51 pg/ml) in HSP group was significantly lower than the control group (38.51±12.86 pg/ml) (P<0.01). In the HSP group, the expression level of Thl7 cells was positively correlated with IL-17A,IL-6,STAT3mRNA and the correlation coefficient was 0.945 (P<0.01),0.864(P<0.01),0.912(P<0.01) respectively.The positive correlation also was showed between the expression levels of Treg cells and IL-2,STAT5 mRNA,the correlation coefficient was 0.967 (P<0.01) and 0.969(P<0.01) respectively. Conclusion:There were higher expression levels of Th17 cells and lower expression levels of Treg cells of children with HSP in acute phase, which showed that Th17/Treg imbalance existed in children with HSP in acute phase.IL-6/STAT3 signaling pathway was activated and the expression level of Th17 cell was positively correlated with the expression level of IL-6 and STAT3 mRNA, prompting that the activation of IL-6/STAT3 signaling pathway may promote the proliferation and activation of Th17 cells. The high expression of Th17 cells caused excessive immune inflammation.At the same time, IL-2/STAT5 signaling pathway was inhibited and the expression level of Treg cells showed also positively correlated with the expression level of IL-2 and STAT5mRNA, prompting that the inhibition of IL-2/STAT5 signaling pathway led to the suppression of Treg cells and the insufficient of immunosuppression function. Both of them may result in extensive small vascular inflammation of the body, which may be one of the causes of HSP pathogenesis. There were increased levels of serum IL-17A IL-6, TGF-β1 and a decreased serum IL-2 in children with acute phase of HSP. Prompt cytokine IL-17A,IL-6,TGF-β1, IL-2 may be involved in the pathogenesis of HSP by adjusting the balance of Th17/Treg cell and the cytokine microenvironment abnormality caused by the abnormal secretion of IL-17A,IL-6,TGF-β1, IL-6 may be a key factor for the balance of Th17/Treg cells.This study provided the experimental basis to clarify the molecular mechanism of Th17/Treg cells imbalances. |
PDF Full Text Request