Programmed Necrosis in Immunity and Inflammatory Diseases
Programmed necrosis or necroptosis is a type of cell death regulated by a specific signaling pathway. Hence it is different from necrosis induced by physical trauma. Receptor-interacting protein kinase (RIPK) 1 and RIPK3 play central roles in programmed necrosis by forming a pro-necrotic signaling complex termed the necrosome. Genetic evidence indicates that in concert with the pro-apoptotic molecules FADD and caspase-8, RIPK1 and RIPK3 regulate embryonic development, T cell clonal expansion, and immune homeostasis. Programmed necrosis contributes to innate immune host defense against certain viruses. The importance of programmed necrosis as a host defense mechanism is highlighted by discovery of viral inhibitors of necrosis. Emerging evidence suggests that programmed necrosis is also involved in bacterial infections and may even directly regulate inflammatory cytokine expression. In this chapter, we discuss how the RIP kinases contribute to different inflammatory diseases.
KeywordsPancreatitis Interferon Fibril Hydrolase Bonnet
We thank members of the Chan Lab and many colleagues for discussion and ideas. This work is supported by grants from the NIH (AI083497 and AI088502). K.M. is supported by a postdoctoral fellowship from the Japan Society for the Promotion of Science.
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