Expression And Significance Of Th17 Cells And Treg Cells In Peripheral Blood Of Patients With Systemic Lupus Erythematosus

BackgroundSystemic lupus erythematosus(SLE) is an autoimmune disease with multi-organ damaged. Its pathogenesis and production of autoantibodies are dependent upon CD4+ T cells.With antigen stimulation, naive CD4+ cells can be differentiated into four different subsets based on the patterns of cytokine present in the local environment. Th17 cells and regulatory T cells (Tregs) have been described as two subsets different from Th1 and Th2 cells. Th17 cells which express retinoic acid-related orphan receptorγt (RORγt) play critical roles in the development of autoimmunity by producing IL-17. Tregs which express the transcription factor forkhead box protein P3 (Foxp3), are able to suppress autoimmune processes. Recent evidence has highlighted the role of Th17 cells as effectors of inflammatory responses and the role of Treg cells in the induction and maintenance of immune tolerance as well. But controversial data have been obtained in SLE.The relationship between Th17 cell and Treg cell subpopulations in SLE needs to be further elucidated. The Th17/Treg balance may be important in the pathogenesis of SLE. In order to investigate the significance of Th17 cells and Treg cells in SLE, we detected the expression of Th17 cells and Treg cells in peripheral blood mononuclear cells (PBMCs) by flow cytometric analysis in 50 SLE patients and 20 healthy controls. The correlation between the quantity of Th17 cells ,Treg cells in SLE patients and disease activity were analyzed respectively.The ratio of Th17 cells and Treg cells in PBMCs of SLE patients was also analyzed. ObjectiveTo investigate the expression and significance of Th17 cells and Treg cells in peripheral blood of patients with systemic lupus erythematosus.MethodsThirty active SLE patients (including 17 SLE patients with nephritis),twenty inactive SLE patients and twenty healthy controls were enrolled in this study. The expression of Th17 cells and Treg cells in PBMCs was evaluated by flow cytometric analysis. The correlation between the quantity of Th17 cells ,Treg cells in SLE patients and disease activity,which was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI),were analyzed respectively.The ratio of Th17 cells and Treg cells in PBMCs of SLE patients was also analyzed.Results1. Test results of Th17 cells: (1)The expression of Th17 cells in peripheral blood: (CD4+IL17+Th17 cells/CD4+T cells):The expression of Th17 cells in PBMCs of SLE patients was higher than that in healthy controls[(1.39±0.60)%VS(0.80±0.33)%, P<0.001]. The expression of Th17 cells in PBMCs of active SLE patients was also higher than those of inactive SLE and healthy controls [(1.68±0.57)%VS( 0.96±0.32)%,P<0.001;(1.68±0.57)%VS(0.80±0.33)% ,P<0.001].While there were no statistical differences between the inactive SLE and healthy controls.Among 30 active SLE patients, patients with lupus nephritis (LN) had higher expression of Th17 cells in PBMCs than SLE patients without nephritis [(1.88±0.54)%VS(1.42±0.51)%,P=0.026]. (2)The correlations between the expression of Th17 cells in peripheral blood and disease activity and other laboratory parameters:The expression of Th17 cells in PBMCs was positively correlated with the SLEDAI score(r=0.67,P<0.001),and negatively correlated with complement C3,C4(r=-0.46,P=0.001 &r=-0.44,P=0.001). But there were no statistical correlation between expression of Th17 cells and titers of ds-DNA antibody.2. Test results of CD4+CD25+Foxp3+T cells:(1)The expression of CD4+CD25+Foxp3+T cells in peripheral blood: ( CD4+CD25+Foxp3+T cells /CD4+T cells): The expression of CD4+CD25+Foxp3+T cells in PBMCs SLE patients was lower than that in healthy controls[(3.09±1.54)%VS(6.04±1.49)%, P<0.001]. The expression of CD4+CD25+Foxp3+T cells in PBMCs of active SLE patients was lower than those of inactive SLE and healthy controls [(2.05±0.65)%VS(4.64±1.13 ) %,P<0.001; ( 2.05±0.65 ) %VS(6.04±1.49)%,P<0.001].And the expression of CD4+CD25+Foxp3+T cells in PBMCs of inactive SLE was also lower than that of healthy controls [(4.64±1.13)%VS(6.04±1.49)%, P=0.002]. Among 30 active SLE patients, patients with LN had lower expression of CD4+CD25+Foxp3+T cells than SLE patients without LN [(1.84±0.59)%VS(2.33±0.64)%, P=0.042].(2)The correlation between the expression of CD4+CD25+Foxp3+T cells in peripheral blood and disease activity and other laboratory parameters: The expression of CD4+CD25+Foxp3+T cells was negatively correlated with the SLEDAI score(r=-0.79,P<0.001),and positively correlated with complement C3,C4(r=0.67,P<0.001 &r=0.53,P<0.001). But there were no statistical correlation between expression of CD4+CD25+Foxp3+T cells and titers of ds-DNA antibody. 3. The ratio of Th17 cells and Treg cells in peripheral blood: The ratio of Th17 cells and Treg cells in PBMCs of patients with active SLE was higher than those of inactive SLE and healthy controls[(0.91±0.43)VS(0.21±0.07),P<0.001;(0.91±0.43)VS(0.13±0.07)%,P<0.001]. The ratio of Th17 cells and Treg cells in PBMCs of SLE patients was also positively correlated with the SLEDAI score(r=0.75,P<0.001).ConclusionThere is an abnormal elevation of Th17 cells and decrease of CD4+CD25+Foxp3+T cells in PBMCs of SLE patients. The imbalance between Th17 cells and CD4+CD25+FoxP3+ Treg cells may play a critical role in the pathogenesis of SLE.