The contribution of NF-κB signalling to immune regulation and tolerance

European Journal of Clinical Investigation

Volumn 45, Issue 5, 2015, Pages 529-539

  van Delft, Myrthe A M ^a   Huitema, Leonie F A ^a   Tas, Sander W ^a  

^a UNIVERSITY OF AMSTERDAM   (Netherlands)

Author keywords

AIRE; Immune regulation; Lymphoid organs; NF B; Tissue specific antigens; Tolerance

Indexed keywords

AUTOIMMUNE REGULATOR PROTEIN; CD40 LIGAND; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; OSTEOCLAST DIFFERENTIATION FACTOR; TUMOR NECROSIS FACTOR RECEPTOR; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 2; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 3;

ANTIGEN PRESENTATION; ANTIGEN PRESENTING CELL; ARTICLE; AUTOIMMUNE DISEASE; AUTOIMMUNITY; CELL INTERACTION; DENDRITIC CELL; GENETIC TRANSCRIPTION; HUMAN; IMMUNOLOGICAL TOLERANCE; IMMUNOREGULATION; LYMPHOID ORGAN; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; SIGNAL TRANSDUCTION; THYMUS; ANIMAL; IMMUNOLOGY; LYMPHOID TISSUE; MOUSE; T LYMPHOCYTE;

ANIMALS; AUTOIMMUNE DISEASES; DENDRITIC CELLS; HUMANS; IMMUNE TOLERANCE; LYMPHOID TISSUE; MICE; NF-KAPPA B; SIGNAL TRANSDUCTION; T-LYMPHOCYTES; T-LYMPHOCYTES, REGULATORY;

EID: 84928338081     PISSN: 00142972     EISSN: 13652362     Source Type: Journal    
DOI: 10.1111/eci.12430     Document Type: Article

References (89)

1. Metzger TC, Anderson MS. Control of central and peripheral tolerance by Aire. Immunol Rev 2011;241:89-103.
2. Drayton DL, Liao S, Mounzer RH, Ruddle NH. Lymphoid organ development: from ontogeny to neogenesis. Nat Immunol 2006;7:344-53.
3. Mathis D, Benoist C. Aire. Annu Rev Immunol 2009;27:287-312.
4. Bonizzi G, Karin M. The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol 2004;25:280-8.
5. Sun SC. Non-canonical NF-kappaB signaling pathway. Cell Res 2011;21:71-85.
6. Kajiura F, Sun S, Nomura T, Izumi K, Ueno T, Bando Y et al. NF-kappa B-inducing kinase establishes self-tolerance in a thymic stroma-dependent manner. J Immunol 2004;172:2067-75.
7. Lomada D, Liu B, Coghlan L, Hu Y, Richie ER. Thymus medulla formation and central tolerance are restored in IKKalpha-/- mice that express an IKKalpha transgene in keratin 5+ thymic epithelial cells. J Immunol 2007;178:829-37.
8. Akiyama T, Shimo Y, Yanai H, Qin J, Ohshima D, Maruyama Y et al. The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance. Immunity 2008;29:423-37.
9. Rossi SW, Kim MY, Leibbrandt A, Parnell SM, Jenkinson WE, Glanville SH et al. RANK signals from CD4(+)3(-) inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla. J Exp Med 2007;204:1267-72.
10. Zhu M, Chin RK, Christiansen PA, Lo JC, Liu X, Ware C et al. NF-kappaB2 is required for the establishment of central tolerance through an Aire-dependent pathway. J Clin Invest 2006;116:2964-71.
11. Mouri Y, Nishijima H, Kawano H, Hirota F, Sakaguchi N, Morimoto J et al. NF-kappaB-inducing kinase in thymic stroma establishes central tolerance by orchestrating cross-talk with not only thymocytes but also dendritic cells. J Immunol 2014;193:4356-67.
12. Tas SW, Vervoordeldonk MJ, Hajji N, Schuitemaker JH, van der Sluijs KF, May MJ et al. Noncanonical NF-kappaB signaling in dendritic cells is required for indoleamine 2, 3-dioxygenase (IDO) induction and immune regulation. Blood 2007;110:1540-9.
13. Basak S, Shih VF, Hoffmann A. Generation and activation of multiple dimeric transcription factors within the NF-kappaB signaling system. Mol Cell Biol 2008;28:3139-50.
14. Gray CM, Remouchamps C, McCorkell KA, Solt LA, Dejardin E, Orange JS et al. Noncanonical NF-kappaB signaling is limited by classical NF-kappaB activity. Sci Signal 2014;7:ra13.
15. Lawrence T, Bebien M, Liu GY, Nizet V, Karin M. IKKalpha limits macrophage NF-kappaB activation and contributes to the resolution of inflammation. Nature 2005;434:1138-43.
16. Ishimaru N, Kishimoto H, Hayashi Y, Sprent J. Regulation of naive T cell function by the NF-kappaB2 pathway. Nat Immunol 2006;7:763-72.
17. Marienfeld R, May MJ, Berberich I, Serfling E, Ghosh S, Neumann M. RelB forms transcriptionally inactive complexes with RelA/p65. J Biol Chem 2003;278:19852-60.
18. Xia Y, Chen S, Wang Y, Mackman N, Ku G, Lo D et al. RelB modulation of IkappaBalpha stability as a mechanism of transcription suppression of interleukin-1alpha (IL-1alpha), IL-1beta, and tumor necrosis factor alpha in fibroblasts. Mol Cell Biol 1999;19:7688-96.
19. Klein L, Kyewski B, Allen PM, Hogquist KA. Positive and negative selection of the T cell repertoire: what thymocytes see (and don't see). Nat Rev Immunol 2014;14:377-91.
20. Liston A, Gray DH. Homeostatic control of regulatory T cell diversity. Nat Rev Immunol 2014;14:154-65.
21. Hinterberger M, Aichinger M, da Prazeres CO, Voehringer D, Hoffmann R, Klein L. Autonomous role of medullary thymic epithelial cells in central CD4(+) T cell tolerance. Nat Immunol 2010;11:512-9.
22. Aschenbrenner K, D'Cruz LM, Vollmann EH, Hinterberger M, Emmerich J, Swee LK et al. Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells. Nat Immunol 2007;8:351-8.
23. Proietto AI, van Dommelen S, Zhou P, Rizzitelli A, D'Amico A, Steptoe RJ et al. Dendritic cells in the thymus contribute to T-regulatory cell induction. Proc Natl Acad Sci U S A 2008;105:19869-74.
24. Nagamine K, Peterson P, Scott HS, Kudoh J, Minoshima S, Heino M et al. Positional cloning of the APECED gene. Nat Genet 1997;17:393-8.
25. Anderson MS, Venanzi ES, Klein L, Chen Z, Berzins SP, Turley SJ et al. Projection of an immunological self shadow within the thymus by the aire protein. Science 2002;298:1395-401.
26. Garcia-Lozano JR, Torres-Agrela B, Montes-Cano MA, Ortiz-Fernandez L, Conde-Jaldon M, Teruel M et al. Association of the AIRE gene with susceptibility to rheumatoid arthritis in a European population: a case control study. Arthritis Res Ther 2013;15:R11.
27. Campbell IK, Kinkel SA, Drake SF, van Nieuwenhuijze A, Hubert FX, Tarlinton DM et al. Autoimmune regulator controls T cell help for pathogenetic autoantibody production in collagen-induced arthritis. Arthritis Rheum 2009;60:1683-93.
28. Derbinski J, Schulte A, Kyewski B, Klein L. Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self. Nat Immunol 2001;2:1032-9.
29. Heino M, Peterson P, Sillanpaa N, Guerin S, Wu L, Anderson G et al. RNA and protein expression of the murine autoimmune regulator gene (Aire) in normal, RelB-deficient and in NOD mouse. Eur J Immunol 2000;30:1884-93.
30. Anderson MS, Venanzi ES, Chen Z, Berzins SP, Benoist C, Mathis D. The cellular mechanism of Aire control of T cell tolerance. Immunity 2005;23:227-39.
31. Malchow S, Leventhal DS, Nishi S, Fischer BI, Shen L, Paner GP et al. Aire-dependent thymic development of tumor-associated regulatory T cells. Science 2013;339:1219-24.
32. Perry JS, Lio CW, Kau AL, Nutsch K, Yang Z, Gordon JI et al. Distinct contributions of Aire and antigen-presenting-cell subsets to the generation of self-tolerance in the thymus. Immunity 2014;41:414-26.
33. Fan Y, Rudert WA, Grupillo M, He J, Sisino G, Trucco M. Thymus-specific deletion of insulin induces autoimmune diabetes. EMBO J 2009;28:2812-24.
34. Grupillo M, Gualtierotti G, He J, Sisino G, Bottino R, Rudert WA et al. Essential roles of insulin expression in Aire+ tolerogenic dendritic cells in maintaining peripheral self-tolerance of islet beta-cells. Cell Immunol 2012;273:115-23.
35. Venanzi ES, Gray DH, Benoist C, Mathis D. Lymphotoxin pathway and Aire influences on thymic medullary epithelial cells are unconnected. J Immunol 2007;179:5693-700.
36. Boehm T, Scheu S, Pfeffer K, Bleul CC. Thymic medullary epithelial cell differentiation, thymocyte emigration, and the control of autoimmunity require lympho-epithelial cross talk via LTbetaR. J Exp Med 2003;198:757-69.
37. Chin RK, Lo JC, Kim O, Blink SE, Christiansen PA, Peterson P et al. Lymphotoxin pathway directs thymic Aire expression. Nat Immunol 2003;4:1121-7.
38. Jenkinson SR, Williams JA, Jeon H, Zhang J, Nitta T, Ohigashi I et al. TRAF3 enforces the requirement for T cell cross-talk in thymic medullary epithelial development. Proc Natl Acad Sci U S A 2013;110:21107-12.
39. Desanti GE, Cowan JE, Baik S, Parnell SM, White AJ, Penninger JM et al. Developmentally regulated availability of RANKL and CD40 ligand reveals distinct mechanisms of fetal and adult cross-talk in the thymus medulla. J Immunol 2012;189:5519-26.
40. Hikosaka Y, Nitta T, Ohigashi I, Yano K, Ishimaru N, Hayashi Y et al. The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator. Immunity 2008;29:438-50.
41. Poliani PL, Vermi W, Facchetti F. Thymus microenvironment in human primary immunodeficiency diseases. Curr Opin Allergy Clin Immunol 2009;9:489-95.
42. Akiyama N, Shinzawa M, Miyauchi M, Yanai H, Tateishi R, Shimo Y et al. Limitation of immune tolerance-inducing thymic epithelial cell development by Spi-B-mediated negative feedback regulation. J Exp Med 2014;211:2425-38.
43. Khan IS, Mouchess ML, Zhu ML, Conley B, Fasano KJ, Hou Y et al. Enhancement of an anti-tumor immune response by transient blockade of central T cell tolerance. J Exp Med 2014;211:761-8.
44. Lo IN, Blair HC, Poliani PL, Marrella V, Ficara F, Cassani B et al. Osteopetrosis rescue upon RANKL administration to Rankl(-/-) mice: a new therapy for human RANKL-dependent ARO. J Bone Miner Res 2012;27:2501-10.
45. Shinkura R, Kitada K, Matsuda F, Tashiro K, Ikuta K, Suzuki M et al. Alymphoplasia is caused by a point mutation in the mouse gene encoding Nf-kappa b-inducing kinase. Nat Genet 1999;22:74-7.
46. Yin L, Wu L, Wesche H, Arthur CD, White JM, Goeddel DV et al. Defective lymphotoxin-beta receptor-induced NF-kappaB transcriptional activity in NIK-deficient mice. Science 2001;291:2162-5.
47. Burkly L, Hession C, Ogata L, Reilly C, Marconi LA, Olson D et al. Expression of relB is required for the development of thymic medulla and dendritic cells. Nature 1995;373:531-6.
48. Martin-Gayo E, Sierra-Filardi E, Corbi AL, Toribio ML. Plasmacytoid dendritic cells resident in human thymus drive natural Treg cell development. Blood 2010;115:5366-75.
49. Heino M, Peterson P, Kudoh J, Nagamine K, Lagerstedt A, Ovod V et al. Autoimmune regulator is expressed in the cells regulating immune tolerance in thymus medulla. Biochem Biophys Res Commun 1999;257:821-5.
50. Long M, Park SG, Strickland I, Hayden MS, Ghosh S. Nuclear factor-kappaB modulates regulatory T cell development by directly regulating expression of Foxp3 transcription factor. Immunity 2009;31:921-31.
51. Schmidt-Supprian M, Courtois G, Tian J, Coyle AJ, Israel A, Rajewsky K et al. Mature T cells depend on signaling through the IKK complex. Immunity 2003;19:377-89.
52. Zhu M, Chin RK, Tumanov AV, Liu X, Fu YX. Lymphotoxin beta receptor is required for the migration and selection of autoreactive T cells in thymic medulla. J Immunol 2007;179:8069-75.
53. Guiducci C, Valzasina B, Dislich H, Colombo MP. CD40/CD40L interaction regulates CD4+CD25+ T reg homeostasis through dendritic cell-produced IL-2. Eur J Immunol 2005;35:557-67.
54. Spence PJ, Green EA. Foxp3+ regulatory T cells promiscuously accept thymic signals critical for their development. Proc Natl Acad Sci U S A 2008;105:973-8.
55. Chen X, Willette-Brown J, Wu X, Hu Y, Howard OM, Hu Y et al. IKKalpha is required for the homeostasis of regulatory T cells and for the expansion of both regulatory and effector CD4 T cells. FASEB J 2015;29:443-54.
56. Murray SE. Cell-intrinsic role for NF-kappa B-inducing kinase in peripheral maintenance but not thymic development of Foxp3+ regulatory T cells in mice. PLoS ONE 2013;8:e76216.
57. Cowan JE, Parnell SM, Nakamura K, Caamano JH, Lane PJ, Jenkinson EJ et al. The thymic medulla is required for Foxp3+ regulatory but not conventional CD4+ thymocyte development. J Exp Med 2013;210:675-81.
58. Futterer A, Mink K, Luz A, Kosco-Vilbois MH, Pfeffer K. The lymphotoxin beta receptor controls organogenesis and affinity maturation in peripheral lymphoid tissues. Immunity 1998;9:59-70.
59. De Trez C, Schneider K, Potter K, Droin N, Fulton J, Norris PS et al. The inhibitory HVEM-BTLA pathway counter regulates lymphotoxin receptor signaling to achieve homeostasis of dendritic cells. J Immunol 2008;180:238-48.
60. Dougall WC, Glaccum M, Charrier K, Rohrbach K, Brasel K, De ST et al. RANK is essential for osteoclast and lymph node development. Genes Dev 1999;13:2412-24.
61. Kamanaka M, Yu P, Yasui T, Yoshida K, Kawabe T, Horii T et al. Protective role of CD40 in Leishmania major infection at two distinct phases of cell-mediated immunity. Immunity 1996;4:275-81.
62. Kawabe T, Naka T, Yoshida K, Tanaka T, Fujiwara H, Suematsu S et al. The immune responses in CD40-deficient mice: impaired immunoglobulin class switching and germinal center formation. Immunity 1994;1:167-78.
63. Miyawaki S, Nakamura Y, Suzuka H, Koba M, Yasumizu R, Ikehara S et al. A new mutation, aly, that induces a generalized lack of lymph nodes accompanied by immunodeficiency in mice. Eur J Immunol 1994;24:429-34.
64. Tamura C, Nakazawa M, Kasahara M, Hotta C, Yoshinari M, Sato F et al. Impaired function of dendritic cells in alymphoplasia (aly/aly) mice for expansion of CD25+CD4+ regulatory T cells. Autoimmunity 2006;39:445-53.
65. Drayton DL, Bonizzi G, Ying X, Liao S, Karin M, Ruddle NH. I kappa B kinase complex alpha kinase activity controls chemokine and high endothelial venule gene expression in lymph nodes and nasal-associated lymphoid tissue. J Immunol 2004;173:6161-8.
66. Weih F, Carrasco D, Durham SK, Barton DS, Rizzo CA, Ryseck RP et al. Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-kappa B/Rel family. Cell 1995;80:331-40.
67. O'Sullivan BJ, Pai S, Street S, An X, MacDonald KP, Wong M et al. Immunotherapy with costimulatory dendritic cells to control autoimmune inflammation. J Immunol 2011;187:4018-30.
68. Wu L, D'Amico A, Winkel KD, Suter M, Lo D, Shortman K. RelB is essential for the development of myeloid-related CD8alpha- dendritic cells but not of lymphoid-related CD8alpha+ dendritic cells. Immunity 1998;9:839-47.
69. Franzoso G, Carlson L, Poljak L, Shores EW, Epstein S, Leonardi A et al. Mice deficient in nuclear factor (NF)-kappa B/p52 present with defects in humoral responses, germinal center reactions, and splenic microarchitecture. J Exp Med 1998;187:147-59.
70. Lo JC, Basak S, James ES, Quiambo RS, Kinsella MC, Alegre ML et al. Coordination between NF-kappaB family members p50 and p52 is essential for mediating LTbetaR signals in the development and organization of secondary lymphoid tissues. Blood 2006;107:1048-55.
71. Alcamo E, Hacohen N, Schulte LC, Rennert PD, Hynes RO, Baltimore D. Requirement for the NF-kappaB family member RelA in the development of secondary lymphoid organs. J Exp Med 2002;195:233-44.
72. Orange JS, Jain A, Ballas ZK, Schneider LC, Geha RS, Bonilla FA. The presentation and natural history of immunodeficiency caused by nuclear factor kappaB essential modulator mutation. J Allergy Clin Immunol 2004;113:725-33.
73. Peters JH, Koenen HJ, Fasse E, Tijssen HJ, Ijzermans JN, Groenen PJ et al. Human secondary lymphoid organs typically contain polyclonally-activated proliferating regulatory T cells. Blood 2013;122:2213-23.
74. Poliani PL, Kisand K, Marrella V, Ravanini M, Notarangelo LD, Villa A et al. Human peripheral lymphoid tissues contain autoimmune regulator-expressing dendritic cells. Am J Pathol 2010;176:1104-12.
75. Pontynen N, Strengell M, Sillanpaa N, Saharinen J, Ulmanen I, Julkunen I et al. Critical immunological pathways are downregulated in APECED patient dendritic cells. J Mol Med (Berl) 2008;86:1139-52.
76. Adamson KA, Pearce SH, Lamb JR, Seckl JR, Howie SE. A comparative study of mRNA and protein expression of the autoimmune regulator gene (Aire) in embryonic and adult murine tissues. J Pathol 2004;202:180-7.
77. Gardner JM, Devoss JJ, Friedman RS, Wong DJ, Tan YX, Zhou X et al. Deletional tolerance mediated by extrathymic Aire-expressing cells. Science 2008;321:843-7.
78. Gardner JM, Metzger TC, McMahon EJ, Au-Yeung BB, Krawisz AK, Lu W et al. Extrathymic Aire-expressing cells are a distinct bone marrow-derived population that induce functional inactivation of CD4(+) T cells. Immunity 2013;39:560-72.
79. Hubert FX, Kinkel SA, Webster KE, Cannon P, Crewther PE, Proeitto AI et al. A specific anti-Aire antibody reveals aire expression is restricted to medullary thymic epithelial cells and not expressed in periphery. J Immunol 2008;180:3824-32.
80. Lee JW, Epardaud M, Sun J, Becker JE, Cheng AC, Yonekura AR et al. Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self. Nat Immunol 2007;8:181-90.
81. Guerau-de-Arellano M, Mathis D, Benoist C. Transcriptional impact of Aire varies with cell type. Proc Natl Acad Sci U S A 2008;105:14011-6.
82. Ramsey C, Winqvist O, Puhakka L, Halonen M, Moro A, Kampe O et al. Aire deficient mice develop multiple features of APECED phenotype and show altered immune response. Hum Mol Genet 2002;11:397-409.
83. Chang JH, Xiao Y, Hu H, Jin J, Yu J, Zhou X et al. Ubc13 maintains the suppressive function of regulatory T cells and prevents their conversion into effector-like T cells. Nat Immunol 2012;13:481-90.
84. Neyt K, Perros F, GeurtsvanKessel CH, Hammad H, Lambrecht BN. Tertiary lymphoid organs in infection and autoimmunity. Trends Immunol 2012;33:297-305.
85. Manzo A, Paoletti S, Carulli M, Blades MC, Barone F, Yanni G et al. Systematic microanatomical analysis of CXCL13 and CCL21 in situ production and progressive lymphoid organization in rheumatoid synovitis. Eur J Immunol 2005;35:1347-59.
86. Kratz A, Campos-Neto A, Hanson MS, Ruddle NH. Chronic inflammation caused by lymphotoxin is lymphoid neogenesis. J Exp Med 1996;183:1461-72.
87. Klimiuk PA, Goronzy JJ, Bjor NJ, Beckenbaugh RD, Weyand CM. Tissue cytokine patterns distinguish variants of rheumatoid synovitis. Am J Pathol 1997;151:1311-9.
88. van de Pavert SA, Mebius RE. New insights into the development of lymphoid tissues. Nat Rev Immunol 2010;10:664-74.
89. Noort AR, Tak PP, Tas SW. Non-canonical NF-kB signaling in rheumatoid arthritis: Dr Jekyll and Mr Hyde? Arthritis Res Ther 2015;17:15.