LAUSR

Abstract Interleukin (IL)‐35 is a responsive anti‐inflammatory cytokine implicated in different diseases processes. It has been reported that elevated IL‐35 contributed to immunosuppression in chronic hepatitis by modulation of T helper 17 (Th17) and regulatory T cells. However, the role of IL‐35 in acute hepatitis B (AHB) was still not completely elucidated. Thus, in the present study, we analyzed the expression and regulatory activity of IL‐35 to Th17 cells and inflammatory response during acute hepatitis B virus (HBV) infection in both peripheral blood cells isolated from AHB patients and in hydrodynamic induced HBV‐infected mouse model. Plasma IL‐35 level and circulating HBV peptides‐induced Th17 frequency was significantly elevated in AHB patients, and IL‐35 expression negatively correlated with liver inflammation. In vitro IL‐35 stimulation to CD4+ T cells purified from AHB patients down‐regulated HBV peptides‐induced Th17‐phenotype, which presented as reduced IL‐17 and IL‐22 production. In vivo IL‐35 administration dampened liver inflammation in HBV plasmid injected mice, however, did not affect HBV antigens production. This process was accompanied by suppression of natural killer cells and down‐regulation of HBV peptides‐induced Th17 cells in the liver, but did not affect total intrahepatic lymphocytes and other cell subsets numbers or chemokines expression in the liver. In conclusion, the current data indicated that IL‐35 might be a novel mediator associated with hepatocytes damage and liver inflammation by regulating HBV peptides‐induced Th17 cells during acute HBV infection. The potential anti‐inflammatory property of IL‐35 might be pivotal for developing new therapeutic approaches for hepatitis B. HighlightsIL‐35 and HBV peptides‐induced Th17 cells was elevated in AHB patients.In vitro IL‐35 stimulation to CD4+ T cells down‐regulated Th17‐phenotype.In vivo IL‐35 administration dampened liver inflammation in acute HBV infected mouse model.In vivo IL‐35 administration suppressed recruitment of Th17 cells into the liver.