TIPE2 as a potential therapeutic target in chronic viral hepatitis

ABSTRACT

Introduction: 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
• hepatitis B virus
• hepatitis C virus
• viral hepatitis
• caspase-8
• nuclear factor-κB

Article highlights

• TIPE2 is a negative regulator essential for maintaining immune homeostasis via the toll-like receptor and T cell receptor signaling pathways.

• TIPE2 is a caspase-8-binding protein that may inhibit the activating protein-1 and nuclear factor-κB (NF-κB).

• TIPE2 may ultimately promote Fas-induced apoptosis in immune cells.

• TIPE2-caspase-8-NF-κB signaling might serve as a biomarker and a new target for therapeutic intervention in chronic viral hepatitis.

• Potential interventions for breaking immune tolerance under chronic hepatitis B virus infection are necessary.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the grant from the National Natural Science Foundation of China (81201287)