The regulatory effects of interleukin-35 on T helper 17 cells in patients with chronic HBV infection and its clinical significance

WANG Xinwei; YANG Daokun; LIANG Haijun; GAO Haili; WANG Yanping

doi:10.13431/j.cnki.immunol.j.20170155

Abstract：Interleukin (IL)-35 has been demonstrated to play an important role in regulation of immune response in both infectious and autoimmune diseases.The study aimed to investigate the expression of IL-35 in patients with chronic hepatitis B (CHB) and its role in Th17 cells,and to provide experimental evidence for elucidating the immunotolerance and inflammatory response in chronic hepatitis B virus (HBV) infection.A total of 27 CHB patients and 18 healthy individuals were enrolled in this study.IL-35 level in serum were measured by enzyme linked-immunosorbent assay,and Th17 cells proportion was determined by flow cytometry;Th17 cells proportion and Th17-related cytokines were also measured in peripheral blood mononuclear cells with IL-35 stimulation.Moreover,IL-35 levels and Th17 cells frequency were measured in response to antiviral therapy.We found that the serum level of IL-35 was significantly higher in CHB patients (72.95 pg/ml± 15.71 pg/ml) than in healthy individuals (46.35 pg/ml±13.71 pg/ml) (P＜0.000 1),and positively correlated with HBV DNA (P＜0.000 1);HBV peptides induced Th17 cells was also remarkably higher in CHB patients (1.52％±0.46％) than in healthy individuals (0.03％ ±0.01％) (P＜0.000 1),however,there was no significant difference in non-specific Th17 cells between CHB patients and healthy individuals (1.66％±0.42％ vs 1.43％±0.43％,P=0.089).Recombinant human IL-35 stimulation notably down-regulated HBV peptides induced Th17 cells proportion and Th17 secreted cytokines (IL-17 and IL-22) in treatmentnaive CHB patients.Moreover,anti-HBV therapy led to remarkable down-regulation of serum IL-35,but did not affect HBV peptides induced Th17 cells.Meanwhile,recombinant human IL-35 stimulation did not influence HBV peptides induced Th17 cells proportion and Th17 secreted cytokines in CHB patients after 48-week antiviral therapy.The current results revealed that IL-35 might play an important immunosuppressive role in CHB patients,leading to immunotolerance and viral persistence.