a Department of Clinical Laboratory, Qilu Hospital , Shandong University , Jinan , China.
b Department of Neurology , Jinan Central Hospital affiliated to Shandong University , Jinan , China.
Expert Opin Ther Targets. 2019 Jun;23(6):485-493. doi: 10.1080/14728222.2019.1608948. Epub 2019 Apr 22.
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.
肿瘤坏死因子-α诱导蛋白-8 样蛋白 2（TIPE2）通过与半胱天冬酶-8 结合，成为先天和适应性免疫反应的新型负调控因子。TIPE2 和 caspase-8 的结合可以抑制激活蛋白-1（AP-1）和核因子-κB（NF-κB）的活性，最终促进免疫细胞中 Fas 诱导的细胞凋亡。因此，TIPE2-caspase-8-NF-κB 信号通路可能作为生物标志物和治疗干预的潜在靶点。
本文综述了 TIPE2 在免疫稳态调节中的生物学功能，以及 TIPE2 在人类免疫反应中受到调控的潜在机制。还解释了 TIPE2-caspase-8 信号通路在乙型肝炎病毒和丙型肝炎病毒慢性感染中的分子途径。
考虑到 TIPE2 在连接免疫和炎症方面的重要作用，该蛋白可能是慢性病毒性肝炎有前途的治疗靶点。然而，有必要研究阐明 TIPE2 在病毒性肝炎免疫发生中的分子机制，并开发打破慢性乙型肝炎病毒感染免疫耐受的潜在干预措施。需要进一步的研究来了解 TIPE2 如何与 caspase-8 结合。
