Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey

Blood - Tập 119 Số 3 - Trang 651-665 - 2012
Bharat Aggarwal1, Subash C. Gupta1, Ji Hye Kim1
1Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX

Tóm tắt

AbstractAlthough activity that induced tumor regression was observed and termed tumor necrosis factor (TNF) as early as the 1960s, the true identity of TNF was not clear until 1984, when Aggarwal and coworkers reported, for the first time, the isolation of 2 cytotoxic factors: one, derived from macrophages (molecular mass 17 kDa), was named TNF, and the second, derived from lymphocytes (20 kDa), was named lymphotoxin. Because the 2 cytotoxic factors exhibited 50% amino acid sequence homology and bound to the same receptor, they came to be called TNF-α and TNF-β. Identification of the protein sequences led to cloning of their cDNA. Based on sequence homology to TNF-α, now a total of 19 members of the TNF superfamily have been identified, along with 29 interacting receptors, and several molecules that interact with the cytoplasmic domain of these receptors. The roles of the TNF superfamily in inflammation, apoptosis, proliferation, invasion, angiogenesis, metastasis, and morphogenesis have been documented. Their roles in immunologic, cardiovascular, neurologic, pulmonary, and metabolic diseases are becoming apparent. TNF superfamily members are active targets for drug development, as indicated by the recent approval and expanding market of TNF blockers used to treat rheumatoid arthritis, psoriasis, Crohns disease, and osteoporosis, with a total market of more than US $20 billion. As we learn more about this family, more therapeutics will probably emerge. In this review, we summarize the initial discovery of TNF-α, and the insights gained regarding the roles of this molecule and its related family members in normal physiology and disease.

Từ khóa


Tài liệu tham khảo

Bhardwaj, 2003, Receptor-mediated choreography of life and death., J Clin Immunol, 23, 317, 10.1023/A:1025319031417

Gaur, 2003, Regulation of proliferation, survival and apoptosis by members of the TNF superfamily., Biochem Pharmacol, 66, 1403, 10.1016/S0006-2952(03)00490-8

Aggarwal, 2003, Signalling pathways of the TNF superfamily: a double-edged sword., Nat Rev Immunol, 3, 745, 10.1038/nri1184

O'Malley, 1962, Action of bacterial polysaccharide on tumors: II. Damage of Sarcoma 37 by serum of mice treated with Serratia marcescens polysaccharide, and induced tolerance., J Natl Cancer Inst, 29, 1169

Carswell, 1975, An endotoxin-induced serum factor that causes necrosis of tumors., Proc Natl Acad Sci U S A, 72, 3666, 10.1073/pnas.72.9.3666

Aggarwal, 1984, Human lymphotoxin: production by a lymphoblastoid cell line, purification, and initial characterization., J Biol Chem, 259, 686, 10.1016/S0021-9258(17)43716-1

Aggarwal, 1985, Primary structure of human lymphotoxin derived from 1788 lymphoblastoid cell line., J Biol Chem, 260, 2334, 10.1016/S0021-9258(18)89559-X

Aggarwal, 1985, Human tumor necrosis factor: production, purification, and characterization., J Biol Chem, 260, 2345, 10.1016/S0021-9258(18)89560-6

Bringman, 1987, Monoclonal antibodies to human tumor necrosis factors alpha and beta: application for affinity purification, immunoassays, and as structural probes., Hybridoma, 6, 489, 10.1089/hyb.1987.6.489

Kelker, 1985, Characterization of human tumor necrosis factor produced by peripheral blood monocytes and its separation from lymphotoxin., Int J Cancer, 36, 69, 10.1002/ijc.2910360112

Pennica, 1984, Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin., Nature, 312, 724, 10.1038/312724a0

Gray, 1984, Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumour necrosis activity., Nature, 312, 721, 10.1038/312721a0

Aggarwal, 1985, Characterization of receptors for human tumour necrosis factor and their regulation by gamma-interferon., Nature, 318, 665, 10.1038/318665a0

Beutler, 1985, Identity of tumour necrosis factor and the macrophage-secreted factor cachectin., Nature, 316, 552, 10.1038/316552a0

Cerami, 2011, The value of failure: the discovery of TNF and its natural inhibitor erythropoietin., J Intern Med, 269, 8, 10.1111/j.1365-2796.2010.02319.x

Schneider, 2003, Identification of a new murine tumor necrosis factor receptor locus that contains two novel murine receptors for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)., J Biol Chem, 278, 5444, 10.1074/jbc.M210783200

Moore, 1999, Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis., Nat Med, 5, 828, 10.1038/10552

Balkwill, 2006, TNF-alpha in promotion and progression of cancer., Cancer Metastasis Rev, 25, 409, 10.1007/s10555-006-9005-3

Deroose, 2011, Long-term results of tumor necrosis factor α- and melphalan-based isolated limb perfusion in locally advanced extremity soft tissue sarcomas., J Clin Oncol, 29, 4036, 10.1200/JCO.2011.35.6618

Deroose, 20 years experience of TNF-based isolated limb perfusion for in-transit melanoma metastases: TNF dose matters [published online ahead of print August 31, 2011]., Ann Surg Oncol

Grunhagen, 2009, Isolated limb perfusion with TNF-alpha and melphalan in locally advanced soft tissue sarcomas of the extremities., Recent Results Cancer Res, 179, 257, 10.1007/978-3-540-77960-5_16

Aggarwal, 2004, Regulation of TRAIL-induced apoptosis by ectopic expression of antiapoptotic factors., Vitam Horm, 67, 453, 10.1016/S0083-6729(04)67023-3

Nikolaev, 2009, APP binds DR6 to trigger axon pruning and neuron death via distinct caspases., Nature, 457, 981, 10.1038/nature07767

Watts, 1999, A casein kinase I motif present in the cytoplasmic domain of members of the tumour necrosis factor ligand family is implicated in “reverse signalling.”, EMBO J, 18, 2119, 10.1093/emboj/18.8.2119

Harashima, 2001, Outside-to-inside signal through the membrane TNF-alpha induces E-selectin (CD62E) expression on activated human CD4+ T cells., J Immunol, 166, 130, 10.4049/jimmunol.166.1.130

Wiley, 1996, Reverse signaling via CD30 ligand., J Immunol, 157, 3635, 10.4049/jimmunol.157.8.3635

Hsu, 1995, The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation., Cell, 81, 495, 10.1016/0092-8674(95)90070-5

Hsu, 1996, TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways., Cell, 84, 299, 10.1016/S0092-8674(00)80984-8

Morgan, 2010, Reactive oxygen species in TNFalpha-induced signaling and cell death., Mol Cells, 30, 1, 10.1007/s10059-010-0105-0

Aggarwal, 2004, Nuclear factor-kappaB: the enemy within., Cancer Cell, 6, 203, 10.1016/j.ccr.2004.09.003

Devin, 2000, The distinct roles of TRAF2 and RIP in IKK activation by TNF-R1: TRAF2 recruits IKK to TNF-R1 while RIP mediates IKK activation., Immunity, 12, 419, 10.1016/S1074-7613(00)80194-6

Natoli, 1997, Tumor necrosis factor (TNF) receptor 1 signaling downstream of TNF receptor-associated factor 2: nuclear factor kappaB (NFkappaB)-inducing kinase requirement for activation of activating protein 1 and NFkappaB but not of c-Jun N-terminal kinase/stress-activated protein kinase., J Biol Chem, 272, 26079, 10.1074/jbc.272.42.26079

Ermolaeva, 2008, Function of TRADD in tumor necrosis factor receptor 1 signaling and in TRIF-dependent inflammatory responses., Nat Immunol, 9, 1037, 10.1038/ni.1638

Desch, 1990, Tumor necrosis factor-alpha exhibits greater proinflammatory activity than lymphotoxin in vitro., Blood, 75, 2030, 10.1182/blood.V75.10.2030.2030

Sugarman, 1985, Recombinant human tumor necrosis factor-alpha: effects on proliferation of normal and transformed cells in vitro., Science, 230, 943, 10.1126/science.3933111

Balkwill, 2009, Tumour necrosis factor and cancer., Nat Rev Cancer, 9, 361, 10.1038/nrc2628

Aggarwal, 2006, Inflammation and cancer: how hot is the link?, Biochem Pharmacol, 72, 1605, 10.1016/j.bcp.2006.06.029

Wiley, 1995, Identification and characterization of a new member of the TNF family that induces apoptosis., Immunity, 3, 673, 10.1016/1074-7613(95)90057-8

Dowlati, 2010, A meta-analysis of cytokines in major depression., Biol Psychiatry, 67, 446, 10.1016/j.biopsych.2009.09.033

Brietzke, 2008, TNF-alpha as a molecular target in bipolar disorder., Prog Neuropsychopharmacol Biol Psychiatry, 32, 1355, 10.1016/j.pnpbp.2008.01.006

Murashima, 2008, Role of cytokines during epileptogenesis and in the transition from the interictal to the ictal state in the epileptic mutant EL mouse., Gene Regul Syst Bio, 2, 267

Swardfager, 2010, A meta-analysis of cytokines in Alzheimer's disease., Biol Psychiatry, 68, 930, 10.1016/j.biopsych.2010.06.012

Nagatsu, 2005, Inflammatory process in Parkinson's disease: role for cytokines., Curr Pharm Des, 11, 999, 10.2174/1381612053381620

Sayed, 2010, Meningeal mast cells affect early T cell central nervous system infiltration and blood-brain barrier integrity through TNF: a role for neutrophil recruitment?, J Immunol, 184, 6891, 10.4049/jimmunol.1000126

Choi, 2002, Fas engagement increases expression of interleukin-6 in human glioma cells., J Neuro-oncol, 56, 13, 10.1023/A:1014467626314

Kapadia, 1995, Tumor necrosis factor-alpha gene and protein expression in adult feline myocardium after endotoxin administration., J Clin Invest, 96, 1042, 10.1172/JCI118090

Levine, 1990, Elevated circulating levels of tumor necrosis factor in severe chronic heart failure., N Engl J Med, 323, 236, 10.1056/NEJM199007263230405

Feldman, 2000, The role of tumor necrosis factor in the pathophysiology of heart failure., J Am Coll Cardiol, 35, 537, 10.1016/S0735-1097(99)00600-2

Diwan, 2003, Inflammatory mediators and the failing heart: a translational approach., Curr Mol Med, 3, 161, 10.2174/1566524033361537

McKellar, 2009, Role for TNF in atherosclerosis? Lessons from autoimmune disease., Nat Rev Cardiol, 6, 410, 10.1038/nrcardio.2009.57

Avina-Zubieta, 2008, Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies., Arthritis Rheum, 59, 1690, 10.1002/art.24092

Matera, 2010, TNF-alpha inhibitors in asthma and COPD: we must not throw the baby out with the bath water., Pulm Pharmacol Ther, 23, 121, 10.1016/j.pupt.2009.10.007

Kips, 1993, The potential role of tumour necrosis factor alpha in asthma., Clin Exp Allergy, 23, 247, 10.1111/j.1365-2222.1993.tb00317.x

Lundblad, 2005, Tumor necrosis factor-alpha overexpression in lung disease: a single cause behind a complex phenotype., Am J Respir Crit Care Med, 171, 1363, 10.1164/rccm.200410-1349OC

Collison, 2009, Emerging role of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) as a key regulator of inflammatory responses., Clin Exp Pharmacol Physiol, 36, 1049, 10.1111/j.1440-1681.2009.05258.x

Schreiber, 2010, Therapeutic Treg expansion in mice by TNFRSF25 prevents allergic lung inflammation., J Clin Invest, 120, 3629, 10.1172/JCI42933

Hotamisligil, 1993, Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance., Science, 259, 87, 10.1126/science.7678183

Tzanavari, 2010, TNF-alpha and obesity., Curr Dir Autoimmun, 11, 145, 10.1159/000289203

Dandona, 2004, Inflammation: the link between insulin resistance, obesity and diabetes., Trends Immunol, 25, 4, 10.1016/j.it.2003.10.013

Vinay, 2011, The tumour necrosis factor/TNF receptor superfamily: therapeutic targets in autoimmune diseases., Clin Exp Immunol, 164, 145, 10.1111/j.1365-2249.2011.04375.x

Banks, 1995, Lymphotoxin-alpha-deficient mice: effects on secondary lymphoid organ development and humoral immune responsiveness., J Immunol, 155, 1685, 10.4049/jimmunol.155.4.1685

Pasparakis, 1996, Immune and inflammatory responses in TNF alpha-deficient mice: a critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response., J Exp Med, 184, 1397, 10.1084/jem.184.4.1397

Marino, 1997, Characterization of tumor necrosis factor-deficient mice., Proc Natl Acad Sci U S A, 94, 8093, 10.1073/pnas.94.15.8093

Hubert, 2009, TRAIL-deficient mice exhibit delayed regression of retinal neovascularization., Am J Pathol, 175, 2697, 10.2353/ajpath.2009.090099

Lamhamedi-Cherradi, 2003, Defective thymocyte apoptosis and accelerated autoimmune diseases in TRAIL−/− mice., Nat Immunol, 4, 255, 10.1038/ni894

Finnberg, 2005, DR5 knockout mice are compromised in radiation-induced apoptosis., Mol Cell Biol, 25, 2000, 10.1128/MCB.25.5.2000-2013.2005

Ida, 2004, A novel mutation (T61I) in the gene encoding tumour necrosis factor receptor superfamily 1A (TNFRSF1A) in a Japanese patient with tumour necrosis factor receptor-associated periodic syndrome (TRAPS) associated with systemic lupus erythematosus., Rheumatology (Oxford), 43, 1292, 10.1093/rheumatology/keh320

Um, 2003, TNF-alpha and TNF-beta gene polymorphisms in cerebral infarction., J Mol Neurosci, 21, 167, 10.1385/JMN:21:2:167

Boyce, 2010, Golimumab: review of the efficacy and tolerability of a recently approved tumor necrosis factor-alpha inhibitor., Clin Ther, 32, 1681, 10.1016/j.clinthera.2010.09.003

Schreiber, 2005, A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn's disease., Gastroenterology, 129, 807, 10.1053/j.gastro.2005.06.064

Hartung, 2010, Atacicept: targeting B cells in multiple sclerosis., Ther Adv Neurol Disord, 3, 205, 10.1177/1756285610371146

Genovese, 2011, Atacicept in patients with rheumatoid arthritis and an inadequate response to tumor necrosis factor antagonist therapy: results of a phase II, randomized, placebo-controlled, dose-finding trial., Arthritis Rheum, 63, 1793, 10.1002/art.30373

van Vollenhoven, 2011, Atacicept in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase II, randomized, placebo-controlled trial., Arthritis Rheum, 63, 1782, 10.1002/art.30372

Singh, 1995, Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected]., J Biol Chem, 270, 24995, 10.1074/jbc.270.42.24995

Chan, 1995, Inhibition of tumor necrosis factor by curcumin, a phytochemical., Biochem Pharmacol, 49, 1551, 10.1016/0006-2952(95)00171-U

Gupta, 2011, Multitargeting by curcumin as revealed by molecular interaction studies, Nat Prod Rep, 28, 1937, 10.1039/c1np00051a

Wua, 2010, Docking prediction for tumor necrosis factor-α and five herbal inhibitors., Intl J Eng Sci Technol, 2, 4263

Sethi, 2008, TNF: a master switch for inflammation to cancer., Front Biosci, 13, 5094, 10.2741/3066

Song, 1997, Tumor necrosis factor (TNF)-mediated kinase cascades: bifurcation of nuclear factor-kappaB and c-jun N-terminal kinase (JNK/SAPK) pathways at TNF receptor-associated factor 2., Proc Natl Acad Sci U S A, 94, 9792, 10.1073/pnas.94.18.9792

Yuasa, 1998, Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38: germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and p38., J Biol Chem, 273, 22681, 10.1074/jbc.273.35.22681

Alimzhanov, 1997, Abnormal development of secondary lymphoid tissues in lymphotoxin beta-deficient mice., Proc Natl Acad Sci U S A, 94, 9302, 10.1073/pnas.94.17.9302

Locksley, 2001, The TNF and TNF receptor superfamilies: integrating mammalian biology., Cell, 104, 487, 10.1016/S0092-8674(01)00237-9

Kim, 2000, Diverse roles of the tumor necrosis factor family member TRANCE in skeletal physiology revealed by TRANCE deficiency and partial rescue by a lymphocyte-expressed TRANCE transgene., Proc Natl Acad Sci U S A, 97, 10905, 10.1073/pnas.200294797

Varfolomeev, 2004, APRIL-deficient mice have normal immune system development., Mol Cell Biol, 24, 997, 10.1128/MCB.24.3.997-1006.2004

Castigli, 2004, Impaired IgA class switching in APRIL-deficient mice., Proc Natl Acad Sci U S A, 101, 3903, 10.1073/pnas.0307348101

Gross, 2001, TACI-Ig neutralizes molecules critical for B cell development and autoimmune disease. impaired B cell maturation in mice lacking BLyS., Immunity, 15, 289, 10.1016/S1074-7613(01)00183-2

Schiemann, 2001, An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway., Science, 293, 2111, 10.1126/science.1061964

Monreal, 1998, Identification of a new splice form of the EDA1 gene permits detection of nearly all X-linked hypohidrotic ectodermal dysplasia mutations., Am J Hum Genet, 63, 380, 10.1086/301984

Schneider, 2001, Mutations leading to X-linked hypohidrotic ectodermal dysplasia affect three major functional domains in the tumor necrosis factor family member ectodysplasin-A., J Biol Chem, 276, 18819, 10.1074/jbc.M101280200

Newton, 2004, Myodegeneration in EDA-A2 transgenic mice is prevented by XEDAR deficiency., Mol Cell Biol, 24, 1608, 10.1128/MCB.24.4.1608-1613.2004

Rothe, 1993, Mice lacking the tumour necrosis factor receptor 1 are resistant to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes., Nature, 364, 798, 10.1038/364798a0

Knight, 2000, Impaired preneoplastic changes and liver tumor formation in tumor necrosis factor receptor type 1 knockout mice., J Exp Med, 192, 1809, 10.1084/jem.192.12.1809

Rieux-Laucat, 1995, Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity., Science, 268, 1347, 10.1126/science.7539157

Jacobson, 1995, Anatomy of autoantibody production: dominant localization of antibody-producing cells to T cell zones in Fas-deficient mice., Immunity, 3, 509, 10.1016/1074-7613(95)90179-5

Singer, 1994, The fas antigen is involved in peripheral but not thymic deletion of T lymphocytes in T cell receptor transgenic mice., Immunity, 1, 365, 10.1016/1074-7613(94)90067-1

Gaspal, 2005, Mice deficient in OX40 and CD30 signals lack memory antibody responses because of deficient CD4 T cell memory., J Immunol, 174, 3891, 10.4049/jimmunol.174.7.3891

Kwon, 2002, Immune responses in 4-1BB (CD137)-deficient mice., J Immunol, 168, 5483, 10.4049/jimmunol.168.11.5483

Vinay, 2004, CD137-deficient mice have reduced NK/NKT cell numbers and function, are resistant to lipopolysaccharide-induced shock syndromes, and have lower IL-4 responses., J Immunol, 173, 4218, 10.4049/jimmunol.173.6.4218

Lee, 2008, Identification of regulatory functions for 4-1BB and 4-1BBL in myelopoiesis and the development of dendritic cells., Nat Immunol, 9, 917, 10.1038/ni.1632

Jeon, 2010, CD137 (4-1BB) deficiency reduces atherosclerosis in hyperlipidemic mice., Circulation, 121, 1124, 10.1161/CIRCULATIONAHA.109.882704

Girgenrath, 2006, TWEAK, via its receptor Fn14, is a novel regulator of mesenchymal progenitor cells and skeletal muscle regeneration., EMBO J, 25, 5826, 10.1038/sj.emboj.7601441

Scholzke, 2011, TWEAK regulates proliferation and differentiation of adult neural progenitor cells., Mol Cell Neurosci, 46, 325, 10.1016/j.mcn.2010.10.004

Tirnitz-Parker, 2010, Tumor necrosis factor-like weak inducer of apoptosis is a mitogen for liver progenitor cells., Hepatology, 52, 291, 10.1002/hep.23663

Yan, 2001, Activation and accumulation of B cells in TACI-deficient mice., Nat Immunol, 2, 638, 10.1038/89790

Yan, 2001, Identification of a novel receptor for B lymphocyte stimulator that is mutated in a mouse strain with severe B cell deficiency., Curr Biol, 11, 1547, 10.1016/S0960-9822(01)00481-X

Wang, 2001, DR3 regulates negative selection during thymocyte development., Mol Cell Biol, 21, 3451, 10.1128/MCB.21.10.3451-3461.2001

Stephens, 2004, Engagement of glucocorticoid-induced TNFR family-related receptor on effector T cells by its ligand mediates resistance to suppression by CD4+CD25+ T cells., J Immunol, 173, 5008, 10.4049/jimmunol.173.8.5008

Pispa, 2008, Edar and Troy signalling pathways act redundantly to regulate initiation of hair follicle development., Hum Mol Genet, 17, 3380, 10.1093/hmg/ddn232

Schmidt, 2003, Enhanced B cell expansion, survival, and humoral responses by targeting death receptor 6., J Exp Med, 197, 51, 10.1084/jem.20020617

Zhao, 2001, Impaired c-Jun amino terminal kinase activity and T cell differentiation in death receptor 6-deficient mice., J Exp Med, 194, 1441, 10.1084/jem.194.10.1441

Liu, 2001, Enhanced CD4+ T cell proliferation and Th2 cytokine production in DR6-deficient mice., Immunity, 15, 23, 10.1016/S1074-7613(01)00162-5

Lee, 1992, Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system., Cell, 69, 737, 10.1016/0092-8674(92)90286-L

Tsitsikov, 2001, TRAF1 is a negative regulator of TNF signaling. enhanced TNF signaling in TRAF1-deficient mice., Immunity, 15, 647, 10.1016/S1074-7613(01)00207-2

Missiou, 2010, Tumor necrosis factor receptor-associated factor 1 (TRAF1) deficiency attenuates atherosclerosis in mice by impairing monocyte recruitment to the vessel wall., Circulation, 121, 2033, 10.1161/CIRCULATIONAHA.109.895037

Nguyen, 1999, TRAF2 deficiency results in hyperactivity of certain TNFR1 signals and impairment of CD40-mediated responses., Immunity, 11, 379, 10.1016/S1074-7613(00)80113-2

Xu, 1996, Targeted disruption of TRAF3 leads to postnatal lethality and defective T-dependent immune responses., Immunity, 5, 407, 10.1016/S1074-7613(00)80497-5

Nakano, 1999, Targeted disruption of Traf5 gene causes defects in CD40- and CD27-mediated lymphocyte activation., Proc Natl Acad Sci U S A, 96, 9803, 10.1073/pnas.96.17.9803

Lomaga, 1999, TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling., Genes Dev, 13, 1015, 10.1101/gad.13.8.1015

Naito, 2002, TRAF6-deficient mice display hypohidrotic ectodermal dysplasia., Proc Natl Acad Sci U S A, 99, 8766, 10.1073/pnas.132636999

Goeddel, 1999, Signal transduction by tumor necrosis factor: the Parker B. Francis Lectureship., Chest, 116, 69S, 10.1378/chest.116.suppl_1.69S

Yeh, 1998, FADD: essential for embryo development and signaling from some, but not all, inducers of apoptosis., Science, 279, 1954, 10.1126/science.279.5358.1954

Kreder, 1999, Impaired neutral sphingomyelinase activation and cutaneous barrier repair in FAN-deficient mice., EMBO J, 18, 2472, 10.1093/emboj/18.9.2472

Varfolomeev, 1998, 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, 9, 267, 10.1016/S1074-7613(00)80609-3

Kelliher, 1998, The death domain kinase RIP mediates the TNF-induced NF-kappaB signal., Immunity, 8, 297, 10.1016/S1074-7613(00)80535-X

Hu, 1999, Abnormal morphogenesis but intact IKK activation in mice lacking the IKKalpha subunit of IkappaB kinase., Science, 284, 316, 10.1126/science.284.5412.316

Li, 1999, The IKKbeta subunit of IkappaB kinase (IKK) is essential for nuclear factor kappaB activation and prevention of apoptosis., J Exp Med, 189, 1839, 10.1084/jem.189.11.1839

Yoshida, 1998, Apaf1 is required for mitochondrial pathways of apoptosis and brain development., Cell, 94, 739, 10.1016/S0092-8674(00)81733-X

Hakem, 1998, Differential requirement for caspase 9 in apoptotic pathways in vivo., Cell, 94, 339, 10.1016/S0092-8674(00)81477-4

Kuida, 1996, Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice., Nature, 384, 368, 10.1038/384368a0

Headon, 2001, Gene defect in ectodermal dysplasia implicates a death domain adapter in development., Nature, 414, 913, 10.1038/414913a

Li, 2008, Act1 modulates autoimmunity through its dual functions in CD40L/BAFF and IL-17 signaling., Cytokine, 41, 105, 10.1016/j.cyto.2007.09.015

Allen, 1993, CD40 ligand gene defects responsible for X-linked hyper-IgM syndrome., Science, 259, 990, 10.1126/science.7679801

Takahashi, 1994, Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand., Cell, 76, 969, 10.1016/0092-8674(94)90375-1

Casal, 2005, Mutation identification in a canine model of X-linked ectodermal dysplasia., Mamm Genome, 16, 524, 10.1007/s00335-004-2463-4

McDermott, 1999, Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes., Cell, 97, 133, 10.1016/S0092-8674(00)80721-7

Waschke, 2005, Tumor necrosis factor receptor gene polymorphisms in Crohn's disease: association with clinical phenotypes., Am J Gastroenterol, 100, 1126, 10.1111/j.1572-0241.2005.40534.x

Magerus-Chatinet, 2011, Onset of autoimmune lymphoproliferative syndrome (ALPS) in humans as a consequence of genetic defect accumulation., J Clin Invest, 121, 106, 10.1172/JCI43752

Hughes, 2000, Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis., Nat Genet, 24, 45, 10.1038/71667

Cundy, 2002, A mutation in the gene TNFRSF11B encoding osteoprotegerin causes an idiopathic hyperphosphatasia phenotype., Hum Mol Genet, 11, 2119, 10.1093/hmg/11.18.2119

Middleton-Hardie, 2006, Deletion of aspartate 182 in OPG causes juvenile Paget's disease by impairing both protein secretion and binding to RANKL., J Bone Miner Res, 21, 438, 10.1359/JBMR.051104

Salzer, 2005, Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans., Nat Genet, 37, 820, 10.1038/ng1600

Mayne, 2008, Systemic autoimmunity in BAFF-R-mutant A/WySnJ strain mice., Eur J Immunol, 38, 587, 10.1002/eji.200737817

Shimomura, 2004, A rare case of hypohidrotic ectodermal dysplasia caused by compound heterozygous mutations in the EDAR gene., J Invest Dermatol, 123, 649, 10.1111/j.0022-202X.2004.23405.x

Perez de Diego, 2010, Human TRAF3 adaptor molecule deficiency leads to impaired Toll-like receptor 3 response and susceptibility to herpes simplex encephalitis., Immunity, 33, 400, 10.1016/j.immuni.2010.08.014