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.
KeywordsMCMV Infection Cell Death Module Necrosis Induction Immune Evasion Gene Macrophage Necrosis
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.
- Bertin J, Armstrong RC, Ottilie S, Martin DA, Wang Y, Banks S, Wang GH, Senkevich TG, Alnemri ES, Moss B et al (1997) Death effector domain-containing herpesvirus and poxvirus proteins inhibit both Fas- and TNFR1-induced apoptosis. Proc Natl Acad Sci U S A 94:1172–1176PubMedCentralPubMedGoogle Scholar
- Cho Y, McQuade T, Zhang HB, Zhang JK, Chan FKM (2011) RIP1-dependent and independent effects of necrostatin-1 in necrosis and T cell activation. PLoS One 6Google Scholar
- Lu JV, Weist BM, van Raam BJ, Marro BS, Nguyen LV, Srinivas P, Bell BD, Luhrs KA, Lane TE, Salvesen GS et al (2011) Complementary roles of Fas-associated death domain (FADD) and receptor interacting protein kinase-3 (RIPK3) in T-cell homeostasis and antiviral immunity. Proc Natl Acad Sci U S A 108:15312–15317PubMedCentralPubMedGoogle Scholar
- Mocarski ES, Upton JW, Kaiser WJ (2012) Viral infection and the evolution of caspase 8-regulated apoptotic and necrotic death pathways. Nat Rev Immunol 12:79–88Google Scholar
- Snow AL, Marsh RA, Krummey SM, Roehrs P, Young LR, Zhang K, van Hoff J, Dhar D, Nichols KE, Filipovich AH et al (2009) Restimulation-induced apoptosis of T cells is impaired in patients with X-linked lymphoproliferative disease caused by SAP deficiency. J Clin Invest 119:2976–2989PubMedCentralPubMedGoogle Scholar
- Takeda K, Komuro Y, Hayakawa T, Oguchi H, Ishida Y, Murakami S, Noguchi T, Kinoshita H, Sekine Y, Iemura S et al (2009) Mitochondrial phosphoglycerate mutase 5 uses alternate catalytic activity as a protein serine/threonine phosphatase to activate ASK1. Proc Natl Acad Sci U S A 106:12301–12305PubMedCentralPubMedGoogle Scholar
- Trichonas G, Murakami Y, Thanos A, Morizane Y, Kayama M, Debouck CM, Hisatomi T, Miller JW, Vavvas DG (2010) Receptor interacting protein kinases mediate retinal detachment-induced photoreceptor necrosis and compensate for inhibition of apoptosis. Proc Natl Acad Sci U S A 107(50):21695–21700PubMedCentralPubMedGoogle Scholar
- Vanlangenakker N, Vanden Berghe T, Bogaert P, Laukens B, Zobel K, Deshayes K, Vucic D, Fulda S, Vandenabeele P, Bertrand MJ (2011) cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent reactive oxygen species production. Cell Death Differ 18:656–665PubMedCentralPubMedGoogle Scholar
- Yang H, Hreggvidsdottir HS, Palmblad K, Wang H, Ochani M, Li J, Lu B, Chavan S, Rosas-Ballina M, Al-Abed Y et al (2010) A critical cysteine is required for HMGB1 binding to Toll-like receptor 4 and activation of macrophage cytokine release. Proc Natl Acad Sci U S A 107:11942–11947PubMedCentralPubMedGoogle Scholar