Skip to main content
SpringerLink
Log in

Programmed Necrosis/Necroptosis: An Inflammatory Form of Cell Death

  • Chapter
  • First Online:
Cell Death

Abstract

It was not long ago when necrosis was thought to be cell injury caused by nonspecific physical trauma. In recent years, a dedicated pathway that triggers necrosis in response to TNF-like death cytokines, certain toll-like receptors, and in response to viral pathogens was described. Signaling adaptors that contain the RIP homotypic interaction motif (RHIM), such as receptor interacting protein kinase (RIPK) 1 and RIPK3, are key inducers for this form of “regulated” necrosis, often referred to as “programmed necrosis” or “necroptosis.” Genetic and biochemical experiments show that RIP kinase-dependent necrosis and caspase-dependent apoptosis are intimately linked. Unlike apoptosis, necrosis tends to promote inflammation. Emerging evidence indicates that the pro-inflammatory nature of necrosis is a critical driver in a wide range of disease pathologies. In this chapter, I discuss the molecular pathway that controls necrosis and how it contributes to different inflammatory diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972;26(4):239–57.

    PubMed  CAS  Google Scholar 

  2. Schweichel JU, Merker HJ. The morphology of various types of cell death in prenatal tissues. Teratology. 1973;7(3):253–66.

    PubMed  CAS  Google Scholar 

  3. Kono H, Rock KL. How dying cells alert the immune system to danger. Nat Rev Immunol. 2008;8(4):279–89.

    PubMed  CAS  Google Scholar 

  4. Yang H et al. 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. 2010;107(26):11942–7.

    PubMed  CAS  Google Scholar 

  5. Lamkanfi M, Dixit VM. Manipulation of host cell death pathways during microbial infections. Cell Host Microbe. 2010;8(1):44–54.

    PubMed  CAS  Google Scholar 

  6. Vandenabeele P et al. Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat Rev Mol Cell Biol. 2010;11(10):700–14.

    PubMed  CAS  Google Scholar 

  7. Laster SM, Wood JG, Gooding LR. Tumor necrosis factor can induce both apoptic and necrotic forms of cell lysis. J Immunol. 1988;141(8):2629–34.

    PubMed  CAS  Google Scholar 

  8. Vercammen D et al. Inhibition of caspases increases the sensitivity of L929 cells to necrosis mediated by tumor necrosis factor. J Exp Med. 1998;187(9):1477–85.

    PubMed  CAS  Google Scholar 

  9. Vercammen D et al. Dual signaling of the Fas receptor: initiation of both apoptotic and necrotic cell death pathways. J Exp Med. 1998;188(5):919–30.

    PubMed  CAS  Google Scholar 

  10. Holler N et al. Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol. 2000;1(6):489–95.

    PubMed  CAS  Google Scholar 

  11. Ch’en IL et al. Antigen-mediated T cell expansion regulated by parallel pathways of death. Proc Natl Acad Sci U S A. 2008;105(45):17463–8.

    PubMed  Google Scholar 

  12. Ch’en IL et al. Mechanisms of necroptosis in T cells. J Exp Med. 2011;208(4):633–41.

    PubMed  Google Scholar 

  13. Cho Y et al. RIP1-dependent and independent effects of necrostatin-1 in necrosis and T cell activation. PloS One. 2011;6(8):e23209.

    PubMed  CAS  Google Scholar 

  14. He S et al. Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3-mediated pathway. Proc Natl Acad Sci U S A. 2011;108(50):20054–9.

    PubMed  CAS  Google Scholar 

  15. Fortes GB et al. Heme induces programmed necrosis on macrophages through autocrine TNF and ROS production. Blood. 2012;119(10):2368–75.

    PubMed  CAS  Google Scholar 

  16. McComb S et al. cIAP1 and cIAP2 limit macrophage necroptosis by inhibiting Rip1 and Rip3 activation. Cell Death Differ. 2012;19(11):1791–801.

    PubMed  CAS  Google Scholar 

  17. Majno G, Joris I. Apoptosis, oncosis, and necrosis. An overview of cell death. Am J Pathol. 1995;146(1):3–15.

    PubMed  CAS  Google Scholar 

  18. Carswell EA et al. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A. 1975;72(9):3666–70.

    PubMed  CAS  Google Scholar 

  19. Chan FK et al. A role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses. J Biol Chem. 2003;278(51):51613–21.

    PubMed  CAS  Google Scholar 

  20. Cho YS et al. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell. 2009;137(6):1112–23.

    PubMed  CAS  Google Scholar 

  21. He S et al. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-α. Cell. 2009;137(6):1100–11.

    PubMed  CAS  Google Scholar 

  22. Zhang DW et al. RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science. 2009;325(5938):332–6.

    PubMed  CAS  Google Scholar 

  23. Micheau O, Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell. 2003;114(2):181–90.

    PubMed  CAS  Google Scholar 

  24. Ea CK et al. Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO. Mol Cell. 2006;22(2):245–57.

    PubMed  CAS  Google Scholar 

  25. Li H et al. Ubiquitination of RIP is required for tumor necrosis factor alpha-induced NF-kappaB activation. J Biol Chem. 2006;281(19):13636–43.

    PubMed  CAS  Google Scholar 

  26. Dynek JN et al. c-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signalling. EMBO J. 2010;29(24):4198–209.

    PubMed  CAS  Google Scholar 

  27. Gerlach B et al. Linear ubiquitination prevents inflammation and regulates immune signalling. Nature. 2011;471(7340):591–6.

    PubMed  CAS  Google Scholar 

  28. O’Donnell MA et al. Ubiquitination of RIP1 regulates an NF-kappaB-independent cell-death switch in TNF signaling. Curr Biol. 2007;17(5):418–24.

    PubMed  Google Scholar 

  29. O’Donnell MA et al. NEMO inhibits programmed necrosis in an NFkappaB-independent manner by restraining RIP1. PloS One. 2012;7(7):e41238.

    PubMed  Google Scholar 

  30. Hitomi J et al. Identification of a molecular signaling network that regulates a cellular necrotic cell death pathway. Cell. 2008;135(7):1311–23.

    PubMed  CAS  Google Scholar 

  31. Vanlangenakker N et al. cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent reactive oxygen species production. Cell Death Differ. 2011;18(4):656–65.

    PubMed  CAS  Google Scholar 

  32. Kawahara A et al. Caspase-independent cell killing by Fas-associated protein with death domain. J Cell Biol. 1998;143(5):1353–60.

    PubMed  CAS  Google Scholar 

  33. Vanden Berghe T et al. Differential signaling to apoptotic and necrotic cell death by Fas-associated death domain protein FADD. J Biol Chem. 2004;279(9):7925–33.

    PubMed  CAS  Google Scholar 

  34. Lin Y et al. Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis. Genes Dev. 1999;13(19):2514–26.

    PubMed  CAS  Google Scholar 

  35. Feng S et al. Cleavage of RIP3 inactivates its caspase-independent apoptosis pathway by removal of kinase domain. Cell Signal. 2007;19(10):2056–67.

    PubMed  CAS  Google Scholar 

  36. O’Donnell MA et al. Caspase 8 inhibits programmed necrosis by processing CYLD. Nat Cell Biol. 2011;13(12):1437–42.

    PubMed  Google Scholar 

  37. Sun X et al. Identification of a novel homotypic interaction motif required for the phosphorylation of receptor-interacting protein (RIP) by RIP3. J Biol Chem. 2002;277(11):9505–11.

    PubMed  CAS  Google Scholar 

  38. Degterev A et al. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol. 2005;1(2):112–9.

    PubMed  CAS  Google Scholar 

  39. Degterev A et al. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol. 2008;4(5):313–21.

    PubMed  CAS  Google Scholar 

  40. Li J et al. The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis. Cell. 2012;150(2):339–50.

    PubMed  CAS  Google Scholar 

  41. Moquin D, Chan FK. The molecular regulation of programmed necrotic cell injury. Trends Biochem Sci. 2010;35(8):434–41.

    PubMed  CAS  Google Scholar 

  42. Eisenberg D, Jucker M. The amyloid state of proteins in human diseases. Cell. 2012;148(6):1188–203.

    PubMed  CAS  Google Scholar 

  43. Sun L et al. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell. 2012;148(1–2):213–27.

    PubMed  CAS  Google Scholar 

  44. Zhao J et al. Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis. Proc Natl Acad Sci USA. 2012; 109(14):5322–7.

    PubMed  CAS  Google Scholar 

  45. Wang Z et al. The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. Cell. 2012;148(1–2):228–43.

    PubMed  CAS  Google Scholar 

  46. Lo SC, Hannink M. PGAM5 tethers a ternary complex containing Keap1 and Nrf2 to mitochondria. Exp Cell Res. 2008;314(8):1789–803.

    PubMed  CAS  Google Scholar 

  47. Kalai M et al. Tipping the balance between necrosis and apoptosis in human and murine cells treated with interferon and dsRNA. Cell Death Differ. 2002;9(9):981–94.

    PubMed  CAS  Google Scholar 

  48. Challa S, Chan FK. Going up in flames: necrotic cell injury and inflammatory diseases. Cell Mol Life Sci. 2010;67(19):3241–53.

    PubMed  CAS  Google Scholar 

  49. Reading PC, Khanna A, Smith GL. Vaccinia virus CrmE encodes a soluble and cell surface tumor necrosis factor receptor that contributes to virus virulence. Virology. 2002; 292(2):285–98.

    PubMed  CAS  Google Scholar 

  50. Harte MT et al. The poxvirus protein A52R targets Toll-like receptor signaling complexes to suppress host defense. J Exp Med. 2003;197(3):343–51.

    PubMed  CAS  Google Scholar 

  51. Stack J et al. Vaccinia virus protein A46R targets multiple Toll-like-interleukin-1 receptor adaptors and contributes to virulence. J Exp Med. 2005;201(6):1007–18.

    PubMed  CAS  Google Scholar 

  52. Zhou Q et al. Target protease specificity of the viral serpin CrmA.Analysis of five caspases. J Biol Chem. 1997;272(12):7797–800.

    PubMed  CAS  Google Scholar 

  53. Li M, Beg AA. Induction of necrotic-like cell death by tumor necrosis factor alpha and caspase inhibitors: novel mechanism for killing virus-infected cells. J Virol. 2000; 74(16):7470–7.

    PubMed  CAS  Google Scholar 

  54. Thome M et al. Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors. Nature. 1997;386(6624):517–21.

    PubMed  CAS  Google Scholar 

  55. Hu S et al. A novel family of viral death effector domain-containing molecules that inhibit both CD-95- and tumor necrosis factor receptor-1-induced apoptosis. J Biol Chem. 1997;272(15):9621–4.

    PubMed  CAS  Google Scholar 

  56. Bertin J et al. Death effector domain-containing herpesvirus and poxvirus proteins inhibit both Fas- and TNFR1-induced apoptosis. Proc Natl Acad Sci U S A. 1997;94(4):1172–6.

    PubMed  CAS  Google Scholar 

  57. Mocarski ES, Upton JW, Kaiser WJ. Viral infection and the evolution of caspase 8-regulated apoptotic and necrotic death pathways. Nat Rev Immunol. 2012;12(2):79–88.

    CAS  Google Scholar 

  58. Upton JW, Kaiser WJ, Mocarski ES. Cytomegalovirus M45 cell death suppression requires receptor-interacting protein (RIP) homotypic interaction motif (RHIM)-dependent interaction with RIP1. J Biol Chem. 2008;283(25):16966–70.

    PubMed  CAS  Google Scholar 

  59. Kaiser WJ, Upton JW, Mocarski ES. Receptor-interacting protein homotypic interaction motif-dependent control of NF-kappa B activation via the DNA-dependent activator of IFN regulatory factors. J Immunol. 2008;181(9):6427–34.

    PubMed  CAS  Google Scholar 

  60. Rebsamen M et al. DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB. EMBO Rep. 2009;10(8):916–22.

    PubMed  CAS  Google Scholar 

  61. Upton JW, Kaiser WJ, Mocarski ES. DAI/ZBP1/DLM-1 complexes with RIP3 to mediate virus-induced programmed necrosis that is targeted by murine cytomegalovirus vIRA. Cell Host Microbe. 2012;11(3):290–7.

    PubMed  CAS  Google Scholar 

  62. Upton JW, Kaiser WJ, Mocarski ES. Virus inhibition of RIP3-dependent necrosis. Cell Host Microbe. 2010;7(4):302–13.

    PubMed  CAS  Google Scholar 

  63. Patrone M et al. The human cytomegalovirus UL45 gene product is a late, virion-associated protein and influences virus growth at low multiplicities of infection. J Gen Virol. 2003;84(Pt 12):3359–70.

    PubMed  CAS  Google Scholar 

  64. Duprez L et al. RIP kinase-dependent necrosis drives lethal systemic inflammatory response syndrome. Immunity. 2011;35(6):908–18.

    PubMed  CAS  Google Scholar 

  65. Murakami Y et al. Receptor interacting protein kinase mediates necrotic cone but not rod cell death in a mouse model of inherited degeneration. Proc Natl Acad Sci U S A. 2012;109(36):14598–603.

    PubMed  CAS  Google Scholar 

  66. Kelliher MA et al. The death domain kinase RIP mediates the TNF-induced NF-kappaB signal. Immunity. 1998;8(3):297–303.

    PubMed  CAS  Google Scholar 

  67. Yamamoto M et al. Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling. J Immunol. 2002;169(12):6668–72.

    PubMed  CAS  Google Scholar 

  68. Oshiumi H et al. TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction. Nat Immunol. 2003;4(2):161–7.

    PubMed  CAS  Google Scholar 

  69. Kaiser WJ, Offermann MK. Apoptosis induced by the toll-like receptor adaptor TRIF is dependent on its receptor interacting protein homotypic interaction motif. J Immunol. 2005;174(8):4942–52.

    PubMed  CAS  Google Scholar 

  70. Weber A et al. Proapoptotic signalling through Toll-like receptor-3 involves TRIF-dependent activation of caspase-8 and is under the control of inhibitor of apoptosis proteins in melanoma cells. Cell Death Differ. 2010;17(6):942–51.

    PubMed  CAS  Google Scholar 

  71. Trichonas G et al. Receptor interacting protein kinases mediate retinal detachment-induced photoreceptor necrosis and compensate for inhibition of apoptosis. Proc Natl Acad Sci U S A. 2010;107(50):21695–700.

    PubMed  CAS  Google Scholar 

  72. Smith CC et al. Necrostatin: a potentially novel cardioprotective agent? Cardiovasc Drugs Ther. 2007;21(4):227–33.

    PubMed  CAS  Google Scholar 

  73. Northington FJ et al. Necrostatin decreases oxidative damage, inflammation, and injury after neonatal HI. J Cereb Blood Flow Metab. 2011;31(1):178–89.

    PubMed  CAS  Google Scholar 

  74. Lim SY et al. The cardioprotective effect of necrostatin requires the cyclophilin-D component of the mitochondrial permeability transition pore. Cardiovasc Drugs Ther. 2007;21(6):467–9.

    PubMed  CAS  Google Scholar 

  75. Watters O, O’Connor JJ. A role for tumor necrosis factor-alpha in ischemia and ischemic preconditioning. J Neuroinflammation. 2011;8:87.

    PubMed  CAS  Google Scholar 

  76. Lambertsen KL, Biber K, Finsen B. Inflammatory cytokines in experimental and human stroke. J Cereb Blood Flow Metab. 2012;32(9):1677–98.

    PubMed  CAS  Google Scholar 

  77. Zhang J et al. Fas-mediated apoptosis and activation-induced T-cell proliferation are defective in mice lacking FADD/Mort1. Nature. 1998;392(6673):296–300.

    PubMed  CAS  Google Scholar 

  78. Yeh WC et al. FADD: essential for embryo development and signaling from some, but not all, inducers of apoptosis. Science. 1998;279(5358):1954–8.

    PubMed  CAS  Google Scholar 

  79. Varfolomeev EE et al. Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally. Immunity. 1998;9(2):267–76.

    PubMed  CAS  Google Scholar 

  80. Zhang H et al. Functional complementation between FADD and RIP1 in embryos and lymphocytes. Nature. 2011;471(7338):373–6.

    PubMed  CAS  Google Scholar 

  81. Kaiser WJ et al. RIP3 mediates the embryonic lethality of caspase-8-deficient mice. Nature. 2011;471(7338):368–72.

    PubMed  CAS  Google Scholar 

  82. Oberst A et al. Catalytic activity of the caspase-8-FLIP(L) complex inhibits RIPK3-dependent necrosis. Nature. 2011;471(7338):363–7.

    PubMed  CAS  Google Scholar 

  83. Dillon CP et al. Survival function of the FADD-CASPASE-8-cFLIP(L) complex. Cell Rep. 2012;1(5):401–7.

    PubMed  CAS  Google Scholar 

  84. Kovalenko A et al. Caspase-8 deficiency in epidermal keratinocytes triggers an inflammatory skin disease. J Exp Med. 2009;206(10):2161–77.

    PubMed  CAS  Google Scholar 

  85. Welz PS et al. FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation. Nature. 2011;477(7364):330–4.

    PubMed  CAS  Google Scholar 

  86. Bonnet MC et al. The adaptor protein FADD protects epidermal keratinocytes from necroptosis in vivo and prevents skin inflammation. Immunity. 2011;35(4):572–82.

    PubMed  CAS  Google Scholar 

  87. Damgaard RB et al. The ubiquitin ligase XIAP recruits LUBAC for NOD2 signaling in inflammation and innate immunity. Mol Cell. 2012;46(6):746–58.

    PubMed  CAS  Google Scholar 

  88. Rajput A et al. RIG-I RNA helicase activation of IRF3 transcription factor is negatively regulated by caspase-8-mediated cleavage of the RIP1 protein. Immunity. 2011;34(3):340–51.

    PubMed  CAS  Google Scholar 

  89. Wallach D, Kovalenko A, Kang TB. ‘Necrosome’-induced inflammation: must cells die for it? Trends Immunol. 2011;32(11):505–9.

    PubMed  CAS  Google Scholar 

  90. Meylan E et al. RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation. Nat Immunol. 2004;5(5):503–7.

    PubMed  CAS  Google Scholar 

  91. Cusson-Hermance N et al. Rip1 mediates the Trif-dependent toll-like receptor 3- and 4-induced NF-{kappa}B activation but does not contribute to interferon regulatory factor 3 activation. J Biol Chem. 2005;280(44):36560–6.

    PubMed  CAS  Google Scholar 

  92. Ermolaeva MA et al. Function of TRADD in tumor necrosis factor receptor 1 signaling and in TRIF-dependent inflammatory responses. Nat Immunol. 2008;9(9):1037–46.

    PubMed  CAS  Google Scholar 

  93. Michallet MC et al. TRADD protein is an essential component of the RIG-like helicase antiviral pathway. Immunity. 2008;28(5):651–61.

    PubMed  CAS  Google Scholar 

  94. Newton K, Sun X, Dixit VM. Kinase RIP3 is dispensable for normal NF-kappa Bs, signaling by the B-cell and T-cell receptors, tumor necrosis factor receptor 1, and Toll-like receptors 2 and 4. Mol Cell Biol. 2004;24(4):1464–9.

    PubMed  CAS  Google Scholar 

  95. Kasof GM et al. The RIP-like kinase, RIP3, induces apoptosis and NF-kappaB nuclear translocation and localizes to mitochondria. FEBS Lett. 2000;473(3):285–91.

    PubMed  CAS  Google Scholar 

  96. Sun X et al. RIP3, a novel apoptosis-inducing kinase. J Biol Chem. 1999;274(24):16871–5.

    PubMed  CAS  Google Scholar 

  97. Vince JE et al. Inhibitor of apoptosis proteins limit RIP3 kinase-dependent interleukin-1 activation. Immunity. 2012;36(2):215–27.

    PubMed  CAS  Google Scholar 

  98. Gringhuis SI et al. Dectin-1 is an extracellular pathogen sensor for the induction and processing of IL-1beta via a noncanonical caspase-8 inflammasome. Nat Immunol. 2012;13(3):246–54.

    PubMed  CAS  Google Scholar 

  99. Pierini R et al. AIM2/ASC triggers caspase-8-dependent apoptosis in Francisella-infected caspase-1-deficient macrophages. Cell Death Differ. 2012;19(10):1709–21.

    PubMed  CAS  Google Scholar 

  100. Kayagaki N et al. Non-canonical inflammasome activation targets caspase-11. Nature. 2011;479(7371):117–21.

    PubMed  CAS  Google Scholar 

  101. Rathinam VA et al. TRIF licenses caspase-11-dependent NLRP3 inflammasome activation by gram-negative bacteria. Cell. 2012;150(3):606–19.

    PubMed  CAS  Google Scholar 

  102. Zheng L et al. Induction of apoptosis in mature T cells by tumour necrosis factor. Nature. 1995;377(6547):348–51.

    PubMed  CAS  Google Scholar 

  103. Lenardo M et al. Mature T lymphocyte apoptosis–immune regulation in a dynamic and unpredictable antigenic environment. Annu Rev Immunol. 1999;17:221–53.

    PubMed  CAS  Google Scholar 

  104. Zheng L et al. T cell growth cytokines cause the superinduction of molecules mediating antigen-induced T lymphocyte death. J Immunol. 1998;160(2):763–9.

    PubMed  CAS  Google Scholar 

  105. Watanabe-Fukunaga R et al. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature. 1992;356(6367):314–7.

    PubMed  CAS  Google Scholar 

  106. Lynch DH et al. The mouse Fas-ligand gene is mutated in gld mice and is part of a TNF family gene cluster. Immunity. 1994;1(2):131–6.

    PubMed  CAS  Google Scholar 

  107. Puck JM, Sneller MC. ALPS: an autoimmune human lymphoproliferative syndrome associated with abnormal lymphocyte apoptosis. Semin Immunol. 1997;9(1):77–84.

    PubMed  CAS  Google Scholar 

  108. Zhang Y et al. Conditional Fas-associated death domain protein (FADD): GFP knockout mice reveal FADD is dispensable in thymic development but essential in peripheral T cell homeostasis. J Immunol. 2005;175(5):3033–44.

    PubMed  CAS  Google Scholar 

  109. Chun HJ et al. Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. Nature. 2002;419(6905):395–9.

    PubMed  CAS  Google Scholar 

  110. Su H et al. Requirement for caspase-8 in NF-kappaB activation by antigen receptor. Science. 2005;307(5714):1465–8.

    PubMed  CAS  Google Scholar 

  111. Osborn SL et al. Fas-associated death domain (FADD) is a negative regulator of T-cell receptor-mediated necroptosis. Proc Natl Acad Sci U S A. 2010;107(29):13034–9.

    PubMed  CAS  Google Scholar 

  112. Lu JV et al. 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. 2011;108(37):15312–7.

    PubMed  CAS  Google Scholar 

  113. Beisner DR et al. Cutting edge: innate immunity conferred by B cells is regulated by caspase-8. J Immunol. 2005;175(6):3469–73.

    PubMed  CAS  Google Scholar 

  114. Imtiyaz HZ et al. The Fas-associated death domain protein is required in apoptosis and TLR-induced proliferative responses in B cells. J Immunol. 2006;176(11):6852–61.

    PubMed  CAS  Google Scholar 

  115. Vivarelli MS et al. RIP links TLR4 to Akt and is essential for cell survival in response to LPS stimulation. J Exp Med. 2004;200(3):399–404.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

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).

Author information

Authors and Affiliations

  1. Department of Pathology, Immunology and Virology Program, University of Massachusetts Medical School, Worcester, MA, USA

    Francis Ka-Ming Chan Ph.D.

Authors
  1. Francis Ka-Ming Chan Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Francis Ka-Ming Chan Ph.D. .

Editor information

Editors and Affiliations

  1. Dept. of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA

    Hao Wu

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Chan, F.KM. (2014). Programmed Necrosis/Necroptosis: An Inflammatory Form of Cell Death. In: Wu, H. (eds) Cell Death. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9302-0_10

Download citation

Publish with us

Policies and ethics

Search

Navigation