Roles for TNF-receptor associated factor 3 (TRAF3) in lymphocyte functions

Cytokine & Growth Factor Reviews - Tập 25 - Trang 147-156 - 2014
Zuoan Yi1, Wai Wai Lin2, Laura L. Stunz1, Gail A. Bishop1,2,3,4
1Department of Microbiology, The University of Iowa, USA
2The Graduate Program in Immunology, The University of Iowa, USA
3Department of Internal Medicine, The University of Iowa, USA
4Veterans Affairs Medical Center, Iowa City, IA 52242, USA

Tài liệu tham khảo

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 Xie, 2007, TRAF3 is a critical regulator of B cell homeostasis in secondary lymphoid organs, Immunity, 27, 253, 10.1016/j.immuni.2007.07.012 Gardam, 2008, TRAF2 and TRAF3 signal adapters act cooperatively to control the maturation and survival signals delivered to B cells by the BAFF receptor, Immunity, 28, 391, 10.1016/j.immuni.2008.01.009 Hildebrand, 2011, Roles of TRAF3 and TRAF5 in immune cell function, Immunol Rev, 244, 55, 10.1111/j.1600-065X.2011.01055.x Mackay, 2003, BAFF AND APRIL: a tutorial on B cell survival, Annu Rev Immunol, 21, 231, 10.1146/annurev.immunol.21.120601.141152 Weih, 2001, Essential role of RelB in germinal center and MZ formation and proper expression of homing chemokines, J Immunol, 167, 1909, 10.4049/jimmunol.167.4.1909 Franzoso, 1998, Mice deficient in NF-κB/p52 present with defects in humoral responses, GC reactions, and splenic microarchitecture, J Exp Med, 187, 147, 10.1084/jem.187.2.147 Xie, 2011, TRAF3 is required for T cell-mediated immunity and TCR/CD28 signaling, J Immunol, 186, 143, 10.4049/jimmunol.1000290 Keats, 2007, Promiscuous mutations activate the noncanonical NF-κB pathway in MM, Cancer Cell, 12, 131, 10.1016/j.ccr.2007.07.003 Annunziata, 2007, Frequent engagement of the classical and alternative NF-κB pathways by diverse genetic abnormalities in multiple myeloma, Cancer Cell, 12, 115, 10.1016/j.ccr.2007.07.004 Otto, 2012, Genetic lesions of the TRAF3 and MAP3K14 genes in classical Hodgkin lymphoma, Br J Haematol, 157, 702, 10.1111/j.1365-2141.2012.09113.x Nagel, 2009, Biallelic inactivation of TRAF3 in a subset of B-cell lymphomas with interstitial del(14)(q24.1q32.33), Leukemia, 23, 2153, 10.1038/leu.2009.149 Moore, 2012, Specific deletion of TRAF3 in B lymphocytes leads to B-lymphoma development in mice, Leukemia, 26, 1122, 10.1038/leu.2011.309 Hu, 1994, A novel RING finger protein interacts with the cytoplasmic domain of CD40, J Biol Chem, 269, 30069, 10.1016/S0021-9258(18)43772-6 Cheng, 1995, Involvement of CRAF1, a relative of TRAF, in CD40 signaling, Science, 267, 1494, 10.1126/science.7533327 Hostager, 1999, Cutting edge: contrasting roles of TRAF2 and TRAF3 in CD40-mediated B lymphocyte activation, J Immunol, 162, 6307, 10.4049/jimmunol.162.11.6307 Pullen, 1998, CD40-TRAF interactions: regulation of CD40 signaling through multiple TRAF binding sites and TRAF hetero-oligomerization, Biochemistry, 37, 11836, 10.1021/bi981067q Hostager, 2003, TRAF2-deficient B lymphocytes reveal novel roles for TRAF2 in CD40 signaling, J Biol Chem, 278, 45382, 10.1074/jbc.M306708200 Haxhinasto, 2003, A novel interaction between PKD and TRAFs regulates BCR-CD40 synergy, J Immunol, 171, 4655, 10.4049/jimmunol.171.9.4655 Xie, 2004, Requirement for TRAF3 in signaling by LMP1, but not CD40, in B lymphocytes, J Exp Med, 199, 661, 10.1084/jem.20031255 Bishop, 2001, Signaling by CD40 and its mimics in B cell activation, Immunol Res, 24, 97, 10.1385/IR:24:2:097 Graham, 2010, Differential B lymphocyte regulation by CD40 and its viral mimic, LMP1, Immunol Rev, 237, 226, 10.1111/j.1600-065X.2010.00932.x Bishop, 2002, Mechanisms of TRAF regulation in B lymphocytes, J Leukoc Biol, 72, 19, 10.1189/jlb.72.1.19 Soni, 2007, LMP1 TRAFficking activates growth and survival pathways, Adv Exp Med Biol, 597, 173, 10.1007/978-0-387-70630-6_14 Arcipowski, 2011, Molecular mechanisms of TRAF6 utilization by the oncogenic viral mimic of CD40, LMP1, J Biol Chem, 286, 9948, 10.1074/jbc.M110.185983 Kraus, 2009, TRAF5 is a critical mediator of in vitro signals and in vivo functions of LMP1, the viral oncogenic mimic of CD40, Proc Natl Acad Sci USA, 106, 17140, 10.1073/pnas.0903786106 Wu, 2005, LMP1 protein from EBV is a structural decoy in B lymphocytes for binding to TRAF3, J Biol Chem, 280, 33620, 10.1074/jbc.M502511200 Ardila-Osorio, 1999, Evidence of LMP1–TRAF3 interactions in glycosphingolipid-rich complexes of lymphoblastoid and nasopharyngeal carcinoma cells, Int J Cancer, 81, 645, 10.1002/(SICI)1097-0215(19990517)81:4<645::AID-IJC22>3.0.CO;2-0 Hostager, 2000, Recruitment of CD40, TRAF2 and TRAF3 to membrane microdomains during CD40 signaling, J Biol Chem, 275, 15392, 10.1074/jbc.M909520199 Kaykas, 2001, CD40 and LMP-1 both signal from lipid rafts but LMP-1 assembles a distinct, more efficient signaling complex, EMBO J, 20, 2641, 10.1093/emboj/20.11.2641 Brown, 2001, Differential signaling and TRAF degradation by CD40 and the EBV oncoprotein LMP1, J Exp Med, 193, 943, 10.1084/jem.193.8.943 Moore, 2005, Differential regulation of CD40-mediated TRAF degradation in B lymphocytes, J Immunol, 175, 3780, 10.4049/jimmunol.175.6.3780 Ye, 1999, The structural basis for the recognition of diverse receptor sequences by TRAF2, Mol Cell, 4, 321, 10.1016/S1097-2765(00)80334-2 Graham, 2009, Roles of the TRAF2/3 binding site in differential B cell signaling by CD40 and its oncogenic mimic, LMP1, J Immunol, 183, 2966, 10.4049/jimmunol.0900442 Peters, 2008, A novel polymorphism of the human CD40 receptor with enhanced function, Blood, 112, 1863, 10.1182/blood-2008-02-138925 Peters, 2010, Differential TRAF3 utilization by a variant human CD40 receptor with enhanced signaling, J Immunol, 185, 6555, 10.4049/jimmunol.1000135 Khare, 2001, The role of TALL-1 and APRIL in immune regulation, Trends Immunol, 22, 61, 10.1016/S1471-4906(00)01843-3 Do, 2002, Mechanisms of BLyS action in B cell immunity, Cytokine Growth Factor Rev, 13, 19, 10.1016/S1359-6101(01)00025-9 Cancro, 2004, The BLyS family of ligands and receptors: an archetype for niche-specific homeostatic regulation, Immunol Rev, 202, 237, 10.1111/j.0105-2896.2004.00212.x Xu, 2002, TRAF3 is associated with BAFF-R and negatively regulates BAFF-R-mediated NF-kB activation and IL-10 production, J Immunol, 169, 6883, 10.4049/jimmunol.169.12.6883 Morrison, 2005, An atypical TRAF binding motif of BAFFR mediates induction of the noncanonical NF-κB signaling pathway, J Biol Chem, 280, 10018, 10.1074/jbc.M413634200 Hatzoglou, 2000, TNF receptor family member BCMA associates with TRAF1, TRAF2, and TRAF3 and activates NF-κB, elk-1, JNK, and p38 MAPK, J Immunol, 165, 1322, 10.4049/jimmunol.165.3.1322 Shu, 2000, B cell maturation protein is a receptor for the TNF family member TALL-1, Proc Natl Acad Sci USA, 97, 9156, 10.1073/pnas.160213497 Xia, 2000, TACI is a TRAF-interacting receptor for TALL-1, a TNF family member involved in B cell regulation, J Exp Med, 192, 137, 10.1084/jem.192.1.137 Hildebrand, 2010, A BAFF-R mutation associated with Non-Hodgkin's lymphoma exhibits altered TRAF association and reveals new insights into proximal BAFF-R signaling, J Exp Med, 207, 2569, 10.1084/jem.20100857 Liao, 2004, Regulation of NIK by TRAF3-induced degradation, J Biol Chem, 279, 26243, 10.1074/jbc.M403286200 Lin, 2013, A complex relationship between TRAF3 and non-canonical NF-κB activation in B lymphocytes, Front Immunol, 4, 10.3389/fimmu.2013.00477 Qian, 2004, Act1, a negative regulator in CD40 and BAFF-mediated B cell survival, Immunity, 21, 575, 10.1016/j.immuni.2004.09.001 Claudio, 2009, The adaptor protein CIKS/Act1 is essential for IL-25-mediated allergic airway inflammation, J Immunol, 182, 1617, 10.4049/jimmunol.182.3.1617 Qian, 2007, The adaptor Act1 is required for IL-17-dependent signaling associated with autoimmune and inflammatory disease, Nat Immunol, 8, 247, 10.1038/ni1439 Chang, 2006, Act1 adaptor protein is an immediate and essential signaling component of IL-17R, J Biol Chem, 281, 35603, 10.1074/jbc.C600256200 Zhu, 2010, Modulation of EAE through TRAF3-mediated suppression of IL-17 receptor signaling, J Exp Med, 207, 2647, 10.1084/jem.20100703 Hauer, 2005, TRAF3 serves as an inhibitor of TRAF2/5-mediated activation of the noncanonical NF-κB pathway by TRAF-binding TNFRs, Proc Natl Acad Sci USA, 102, 2874, 10.1073/pnas.0500187102 Rothe, 1995, The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins, Cell, 83, 1243, 10.1016/0092-8674(95)90149-3 Munroe, 2004, Role of TRAF2 in distinct and overlapping CD40 and TNFR2/CD120b-mediated B lymphocyte activation, J Biol Chem, 279, 53222, 10.1074/jbc.M410539200 Hostager, 2002, Role of TRAF2 in the activation of IgM secretion by CD40 and CD120b, J Immunol, 168, 3318, 10.4049/jimmunol.168.7.3318 Peng, 2005, Signaling to B cells by TLRs, Curr Opin Immunol, 17, 230, 10.1016/j.coi.2005.03.003 Fillatreau, 2011, Novel regulatory functions for TLR-activated B cells during intracellular bacterial infection, Immunol Rev, 240, 52, 10.1111/j.1600-065X.2010.00991.x Green, 2011, TLR driven B cell activation in the induction of systemic autoimmunity, Semin Immunol, 23, 106, 10.1016/j.smim.2011.01.016 Aderem, 2000, TLRs in the induction of the innate immune response, Nature, 406, 782, 10.1038/35021228 Häcker, 2006, Specificity in TLR signalling through distinct effector functions of TRAF3 and TRAF6, Nature, 439, 204, 10.1038/nature04369 Oganesyan, 2006, Critical role of TRAF3 in the TLR-dependent and independent antiviral response, Nature, 439, 208, 10.1038/nature04374 Perkins, 2013, Reprogramming of murine macrophages through TLR2 confers viral resistance via TRAF3-mediated, enhanced interferon production, PLoS Pathog, e1003479, 10.1371/journal.ppat.1003479 Pérez de Diego, 2010, Human TRAF3 adaptor molecule deficiency leads to impaired TLR3 response and susceptibility to Herpes simplex encephalitis, Immunity, 33, 400, 10.1016/j.immuni.2010.08.014 Xie, 2011, Enhanced TLR responses of TRAF3-deficient B lymphocytes, J Leukoc Biol, 90, 1149, 10.1189/jlb.0111044 Buchta, 2014, TRAF5 negatively regulates TLR signaling in B lymphocytes, J Immunol, 192, 145, 10.4049/jimmunol.1301901 Sun, 2004, The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes, Mol Cell, 14, 289, 10.1016/S1097-2765(04)00236-9 Xie, 2013, TRAF6 regulates TCR signaling via interaction with and modification of LAT adapter, J Immunol, 190, 4027, 10.4049/jimmunol.1202742 Yi, 2013, TRAF3 plays a key role in the development and function of iNKT cells, J Exp Med, 210, 1079, 10.1084/jem.20122135 Lee, 2001, A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival, Immunity, 15, 763, 10.1016/S1074-7613(01)00227-8 Tanigaki, 2004, Regulation of αβ/γδ T cell lineage commitment and peripheral T cell responses by Notch/RBP-J signaling, Immunity, 20, 611, 10.1016/S1074-7613(04)00109-8 Godfrey, 2010, Raising the NKT cell family, Nat Immunol, 11, 197, 10.1038/ni.1841 Bajenoff, 2002, Repeated antigen exposure is necessary for the differentiation, but not the initial proliferation, of naive CD4+ T cells, J Immunol, 168, 1723, 10.4049/jimmunol.168.4.1723 Matsuoka, 2004, T-bet upregulation and subsequent IL-12 stimulation are essential for induction of Th1 mediated immunopathology in Crohn's disease, Gut, 53, 1303, 10.1136/gut.2003.024190 Matsuda, 2007, Temporal dissection of T-bet functions, J Immunol, 178, 3457, 10.4049/jimmunol.178.6.3457 Townsend, 2004, T-bet regulates the terminal maturation and homeostasis of NK and Vα14i NKT cells, Immunity, 20, 477, 10.1016/S1074-7613(04)00076-7 Bennett, 2001, The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3, Nat Genet, 27, 20, 10.1038/83713 Fontenot, 2003, Foxp3 programs the development and function of CD4+CD25+ regulatory T cells, Nat Immunol, 4, 330, 10.1038/ni904 Khattri, 2003, An essential role for Scurfin in CD4+CD25+ T regulatory cells, Nat Immunol, 4, 337, 10.1038/ni909 Kim, 2007, Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice, Nat Immunol, 8, 191, 10.1038/ni1428 Lahl, 2007, Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease, J Exp Med, 204, 57, 10.1084/jem.20061852 Wortzman, 2013, The contextual role of TNFR family members in CD8+ T-cell control of viral infections, Immunol Rev, 255, 125, 10.1111/imr.12086 Munroe, 2009, Functional roles for T cell CD40 in infection and autoimmune disese: the role of CD40 in lymphocyte homeostasis, Semin Immunol, 21, 283, 10.1016/j.smim.2009.05.008 So, 2012, Regulation of the PKCθ-NF-κB axis in T lymphocytes by the TNF-R family member OX40, Front Immunol, 3, 133, 10.3389/fimmu.2012.00133 Arch, 1998, 4-1BB and Ox40 are members of a TNF-R subfamily that bind TRAFs and activate NF-κB, Mol Cell Biol, 18, 558, 10.1128/MCB.18.1.558 Kawamata, 1998, Activation of OX40 signal transduction pathways leads to TRAF2 and TRAF5-mediated NF-κB activation, J Biol Chem, 273, 5805, 10.1074/jbc.273.10.5808 Takaori-Kondo, 2000, Both amino- and carboxyl-terminal domains of TRAF3 negatively regulate NF-κB activation induced by OX40 signaling, Biochem Biophys Res Commun, 272, 856, 10.1006/bbrc.2000.2860 Song, 2004, The costimulation-regulated duration of PKB activation controls T cell longevity, Nat Immunol, 5, 150, 10.1038/ni1030 Song, 2008, Activation of NF-κB1 by OX40 contributes to antigen-driven T cell expansion and survival, J Immunol, 180, 7240, 10.4049/jimmunol.180.11.7240 So, 2013, Regulation of PI-3 K and Akt signaling in T lymphocytes and other cells by TNFR family molecules, Front Immunol, 4, 139, 10.3389/fimmu.2013.00139 So, 2008, Immune regulation and control of regulatory T cells by OX40 and 4-1BB, Cytokine Growth Factor Rev, J19, 253, 10.1016/j.cytogfr.2008.04.003 Lin, 2013, GITR-dependent regulation of 4-1BB expression: implications for T cell memory and anti-4-1BB-induced pathology, J Immunol, 190, 4627, 10.4049/jimmunol.1201854 Lee, 2003, 4-1BB cross-linking enhances the survival and cell cycle progression of CD4 T lymphocytes, Cell Immunol, 223, 143, 10.1016/S0008-8749(03)00169-2 Lin, 2012, Contribution of 4-1BBL on radioresistant cells in providing survival signals through 4-1BB expressed on CD8+ memory T cells in the bone marrow, Eur J Immunol, 42, 2861, 10.1002/eji.201242503 Jang, 1998, Human 4-1BB (CD137) signals are mediated by TRAF2 and activate NF-κB, Biochem Biophys Res Commun, 242, 613, 10.1006/bbrc.1997.8016 Saoulli, 1998, CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB ligand, J Exp Med, 187, 1849, 10.1084/jem.187.11.1849 McPherson, 2012, Opposing roles for TRAF1 in the alternative versus classical NF-κB pathway in T cells, J Biol Chem, 287, 23010, 10.1074/jbc.M112.350538 Sabbagh, 2006, A critical role for TRAF1 and Bim down-regulation in CD8 memory T cell survival, Proc Natl Acad Sci USA, 103, 18703, 10.1073/pnas.0602919103 Lee, 2002, 4-1BB promotes the survival of CD8+ T lymphocytes by increasing expression of Bcl-xL and Bfl-1, J Immunol, 169, 4882, 10.4049/jimmunol.169.9.4882 Lee do, 2013, 4-1BB signaling activates the TCF-1 effector/β-catenin pathway with delayed kinetics via ERK signaling and delayed PI3 K/AKT activation to promote the proliferation of CD8+ T cells, PLoS ONE, 8, e69677, 10.1371/journal.pone.0069677 Ware, 2009, Targeting the LIGHT–HVEM pathway, Adv Exp Med Biol, 647, 146, 10.1007/978-0-387-89520-8_10 Marsters, 1997, HVEM, a member of the TNFR family, interacts with members of the TRAF family and activates the transcription factors NF-κB and AP-1, J Biol Chem, 272, 14029, 10.1074/jbc.272.22.14029 Soroosh, 2011, HVEM (TNFRSF14) regulates the persistence of T helper memory cell populations, J Exp Med, 208, 797, 10.1084/jem.20101562 Gurney, 1999, Identification of a new member of the TNF family and its receptor, a human ortholog of mouse GITR, Curr Biol, 9, 215, 10.1016/S0960-9822(99)80093-1 Kwon, 1999, Identification of a novel activation-inducible protein of the TNFR superfamily and its ligand, J Biol Chem, 274, 6056, 10.1074/jbc.274.10.6056 Snell, 2010, CD8 T cell-intrinsic GITR is required for T cell clonal expansion and mouse survival following severe influenza infection, J Immunol, 185, 7223, 10.4049/jimmunol.1001912 Kim, 2010, Blockade of GITR–GITRL interaction maintains Treg function to prolong allograft survival, Eur J Immunol, 40, 1369, 10.1002/eji.200940046 Aizawa, 1997, TRAF5 and TRAF2 are involved in CD30-mediated NF-κB activation, J Biol Chem, 272, 2042, 10.1074/jbc.272.4.2042 Boucher, 1997, Binding sites of cytoplasmic effectors TRAF1, 2, and 3 on CD30 and other members of the TNFR superfamily, Biochem Biophys Res Commun, 233, 592, 10.1006/bbrc.1997.6509 Nishimura, 2005, A novel role of CD30/CD30 ligand signaling in the generation of long-lived memory CD8+ T cells, J Immunol, 175, 4627, 10.4049/jimmunol.175.7.4627 Sun, 2010, CD30L/CD30 plays a critical role in Th17 differentiation in mice, J Immunol, 185, 2222, 10.4049/jimmunol.1000024 Reynolds, 2013, TLR regulation of effector T lymphocyte function, Trends Immunol, 34, 511, 10.1016/j.it.2013.06.003 Gelman, 2004, TLR ligands directly promote activated CD4+ T cell survival, J Immunol, 172, 6065, 10.4049/jimmunol.172.10.6065 Reynolds, 2012, TLR4 signaling in T cells promotes autoimmune inflammation, Proc Natl Acad Sci USA, 109, 13064, 10.1073/pnas.1120585109 Liu, 2007, TLRs and immune regulation: their direct and indirect modulation on regulatory CD4+CD25+ T cells, Immunology, 122, 149, 10.1111/j.1365-2567.2007.02651.x Loo, 2011, Immune signaling by RIG-I-like receptors, Immunity, 34, 680, 10.1016/j.immuni.2011.05.003 Nakhaei, 2009, RIG-I-like receptors: sensing and responding to RNA virus infection, Semin Immunol, 21, 215, 10.1016/j.smim.2009.05.001 Saha, 2006, Regulation of antiviral responses by a direct and specific interaction between TRAF3 and Cardif, EMBO J, 25, 3257, 10.1038/sj.emboj.7601220 Nakhaei, 2009, The E3 ubiquitin ligase Triad3A negatively regulates the RIG-I/MAVS signaling pathway by targeting TRAF3 for degradation, PLoS Pathog, 5, e1000650, 10.1371/journal.ppat.1000650 Suthar, 2012, The RIG-I-like receptor LGP2 controls CD8+ T cell survival and fitness, Immunity, 37, 235, 10.1016/j.immuni.2012.07.004 de Jong, 2010, Activation of noncanonical NF-κB signaling by the oncoprotein Tio, J Biol Chem, 285, 16495, 10.1074/jbc.M110.102848 Katsch, 2012, Species restriction of Herpesvirus saimiri and Herpesvirus ateles: human lymphocyte transformation correlates with distinct signaling properties of viral oncoproteins, Virus Res, 165, 179, 10.1016/j.virusres.2012.02.014 Albrecht, 1999, Herpesvirus ateles gene product Tio interacts with nonreceptor protein tyrosine kinases, J Virol, 73, 4631, 10.1128/JVI.73.6.4631-4639.1999 Heinemann, 2006, NFκB signaling is induced by the oncoprotein Tio through direct interaction with TRAF6, J Biol Chem, 281, 8565, 10.1074/jbc.M510891200 de Jong, 2013, Noncanonical NF-κB activation by the oncoprotein Tio occurs through a nonconserved TRAF3-binding motif, Sci Signal, 6, ra27, 10.1126/scisignal.2003309 Albrecht, 2005, Tyrosine phosphorylation of the Tio oncoprotein is essential for transformation of primary human T cells, J Virol, 79, 10507, 10.1128/JVI.79.16.10507-10513.2005 Abraham, 2012, HIV-1 Nef: a multifaceted modulator of TCR signaling, Cell Commun Signal, 10, 39, 10.1186/1478-811X-10-39 Mangino, 2011, HIV-1 Nef induces proinflammatory state in macrophages through its acidic cluster domain: involvement of TRAF2, PLoS ONE, 6, e22982, 10.1371/journal.pone.0022982 Mishra, 2012, HIV-1 Tat C-mediated regulation of TRAF3 by microRNA 32 in human microglia, J Neuroinflamm, 9, 131, 10.1186/1742-2094-9-131 Aya, 2005, NIK controls lymphocyte and osteoclast activities in inflammatory arthritis, J Clin Invest, 115, 1848, 10.1172/JCI23763 Jin, 2009, Regulation of Th17 cell differentiation and EAE induction by MAP3K NIK, Blood, 113, 6603, 10.1182/blood-2008-12-192914 Hofmann, 2011, NIK signaling in DC but not in T cells is required for the development of effector T cells and cell-mediated immune responses, J Exp Med, 208, 1917, 10.1084/jem.20110128 Boehm, 2003, Thymic medullary epithelial cell differentiation, thymocyte emigration, and the control of autoimmunity require lympho-epithelial cross talk via LTβR, J Exp Med, 198, 757, 10.1084/jem.20030794 Zhu, 2006, NF-κB2 is required for the establishment of central tolerance through an Aire-dependent pathway, J Clin Invest, 116, 2964, 10.1172/JCI28326 Elewaut, 2003, NIK-dependent RelB activation defines a unique signaling pathway for the development of Vα 14i NKT cells, J Exp Med, 197, 1623, 10.1084/jem.20030141 Sivakumar, 2003, Differential requirement for Rel/NF-κB family members in NKT cell development, J Exp Med, 197, 1613, 10.1084/jem.20022234 Murray, 2013, Cell-intrinsic role for NIK in peripheral maintenance but not thymic development of Foxp3+ regulatory T cells in mice, PLoS ONE, 8, e76216, 10.1371/journal.pone.0076216 Vallabhapurapu, 2008, Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-κB signaling, Nat Immunol, 9, 1364, 10.1038/ni.1678 Zarnegar, 2008, Noncanonical NF-κB activation requires coordinated assembly of a regulatory complex of the adaptors cIAP1, cIAP2, TRAF2 and TRAF3 and the kinase NIK, Nat Immunol, 9, 1371, 10.1038/ni.1676