Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2) is a novel negative regulator of innate and adaptive immune responses by binding to caspase-8. The binding of TIPE2 and caspase-8 can inhibit the activity of activating protein-1(AP-1) and nuclear factor-κB (NF-κB), ultimately promoting Fas-induced apoptosis in immune cells. Therefore, TIPE2-caspase-8-NF-κB signaling might serve as a biomarker and a potential target for therapeutic intervention. Areas covered: This review summarizes the biological functions of TIPE2 in the regulation of immune homeostasis and the underlying mechanism by which TIPE2 is regulated in the human immune response. The molecular pathway of TIPE2-caspase-8 signaling in chronic infections of hepatitis B virus and hepatitis C virus is also explained. Expert opinion: Considering the essential role of TIPE2 in linking immunity and inflammation, this protein may be a promising therapeutic target in chronic viral hepatitis. However, studies are necessary to elucidate the molecular mechanism of TIPE2 in the immunogenesis of viral hepatitis and to develop potential interventions for breaking immune tolerance in chronic hepatitis B virus infection. Additional studies are required to understand how TIPE2 binds to caspase-8.
Keywords: Tumor necrosis factor-α-induced protein-8 like-2; caspase-8; hepatitis B virus; hepatitis C virus; nuclear factor-κB; viral hepatitis.