Effects of Jauns kinase/signal transducer and activator of transcription 3 signaling pathway on peripheral blood regulatory T cell function and its regulatory mechanism in patients with rheumatoid arthritis / 中华风湿病学杂志

ABSTRACT

Objective To evaluate the function of regulatory T (Treg) cells in peripheral blood from patients with rheumatoid arthritis (RA),and to explore the possible role of the signal transducer and activator of transcription 3 (STAT3) signaling pathway in Treg cell dysfunction.Methods Totally,60 patients with rheumatoid arthritis,were enrolled into this study.Sixty healthy blood donors served as the control group.Peripheral heparin anticoagulant venous blood was collected from 60 patients with RA and 60 healthy controls respectively.Flow cytometry was used to detect the proportion of Treg cells in peripheral blood.Mixed culture of lymphocytes in vitro was used to detect the proliferation of Treg cells and the inhibition of effective T cells (Tresp) in peripheral blood of RA patients and healthy controls.Phosphorylated STAT3 protein and secretion of pro-inflammatory factors (IFN)-γ,Tumor necrosis factors (TNF)-α and interleukin-17A (IL-17A) in Treg cells were tested by flow cytometry and Quantitative Real-time polymerase chain reaction (qRT-PCR).Treg cells of RA patients were handled with STAT3 pathway inhibitor StatticV to observe the recovery of proliferation and inhibition function and the change of secretion of pro-inflammatory factors.The differences between groups were analyzed by analysis of Variance,and Dunnett's test was used to compare the mean of multiple samples.Results Significant differences were observed in the proportion of Treg cells in peripheral blood between the patient group and the control group [(6.51±0.24)％ vs (2.23±0.18)％,t=4.22,P＜0.05].Compared with controlderived Treg cells,the patient-derived Treg cells showed significantly decreased proli-ferative activity and inhibitory effects on Tresp cells,but increased propòrtion of cells secreting p-STAT3,IFN-γ TNF-α and IL-17A (all P＜0.05).After treated with 50 μg/L Stattic V,a significant increase was observed in the inhibitory effect of patient-derived Treg cells on Tresp cells [inhibition rate(61.24±4.62)％ vs (28.15±10.37)％,P＜0.05],but a significant decrease in the mRNA expressions of IFN-γ(2-△△Ct(1.65±0.88) vs (23.32±6.71),P＜0.05],TNF-α (0.85±0.71) vs (4.85±1.53),P＜0.05) and IL-17A (0.57±0.14) vs (3.10±0.62),all P＜0.05] in patientderived Treg cells compared with untreated patient-derived Treg cells.Conclusion The negative regulatory effect of Treg cells on Tresp cells is decreased in patients with rheumatoid arthritis,which may be associated with abnormal activation of the STAT3 signaling pathway,and inhibition of the pathway may restore the function of Treg cells to a certain extent.