摘要
Objective The study aims to investigate the effects of interleukin-2-inducible T-cell kinase(ITK)on hepatitis B virus(HBV)-induced type I interferon(IFN)expression and the antiviral response.Methods Expression of ITK and type I interferon(IFN)were examined in peripheral blood mononuclear cells from 20 healthy volunteers and 45 HBV-infected patients.Mouse primary hepatocytes were treated with the ITK inhibitor ibrutinib to assess the expression of type I IFN after HBV infection in vitro.Mice were treated with ibrutinib and evaluated for its effects on HBV infection in vivo.The effects of type I IFN production were explored in cells with an ITK deletion or a double knockout of ITK and suppressor of cytokine signaling 1(SOCS1)engineered via CRISPR.Results The expression levels of ITK and IFN-βwere upregulated in patients with acute HBV infection.HBV-induced expression of type I IFN was effectively inhibited by treatment with ibrutinib.ITK negatively regulated the expression of SOSC1,whereas inhibiting ITK expression decreased IFN regulatory factor 3 activity and increased SOCS1 expression.In the SOCS1 knockout,the downregulated phenotype of type I IFN expression in ITK-deficient cells was reversed after HBV infection.Conclusion ITK regulated HBV-induced expression of type I IFN by modulating SOCS1.
基金
supported by Quanzhou City Science&Technology Program of China 455(2022NS056)
the Science and Technology Department of Fujian Province(No.2024J01121794).
