Home LiteratureArticle Details
PMID: 20190822 Published · ppublish English Journal Article Review

The complicated role of NF-kappaB in T-cell selection.

Cellular & molecular immunology ·Vol. 7 ·No. 2 ·2010-03-00 ·Pages 89-93

Zhu M, Fu Y

Abstract

The nuclear factor (NF)-kappaB transcription factor family plays important roles in the immune system. Aberrant NF-kappaB signaling is frequently associated with inflammation and autoimmune diseases but the underlying mechanisms are not fully understood. Recent studies show that NF-kappaB plays a critical role in T-cell central tolerance. Two NF-kappaB signaling pathways have been identified: the canonical pathway and the alternative pathway. In the establishment of T-cell central tolerance, the alternative pathway appears to be the key signaling component in thymic stromal cells for their development and function, while the canonical pathway exerts its function more in autonomous T-cell selection. This review intends to summarize the current understanding of the role of NF-kappaB in establishing T-cell central tolerance and highlight unsolved intriguing questions for future work.

MeSH Terms
Animals Cell Differentiation Immune Tolerance NF-kappa B/immunology,metabolism Signal Transduction T-Lymphocytes/cytology,immunology,metabolism
Chemicals
NF-kappa B
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Zhu Mingzhao
CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences (CAS), Beijing, China. zhumz@ibp.ac.cn
Fu Yangxin
References (54)
54 references, click to expand
  1. RANK signals from CD4(+)3(-) inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla.
    J Exp Med. 2007 Jun 11;204(6):1267-72 PMID: 17502664
  2. Control of lymphocyte development by nuclear factor-kappaB.
    Nat Rev Immunol. 2005 Jun;5(6):435-45 PMID: 15905862
  3. CCR7-dependent cortex-to-medulla migration of positively selected thymocytes is essential for establishing central tolerance.
    Immunity. 2006 Feb;24(2):165-77 PMID: 16473829
  4. Lymphotoxin beta receptor is required for the migration and selection of autoreactive T cells in thymic medulla.
    J Immunol. 2007 Dec 15;179(12):8069-75 PMID: 18056347
  5. Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway.
    Science. 2001 Aug 24;293(5534):1495-9 PMID: 11520989
  6. Lymphotoxin pathway and Aire influences on thymic medullary epithelial cells are unconnected.
    J Immunol. 2007 Nov 1;179(9):5693-700 PMID: 17947641
  7. Requirement for NF-kappaB in osteoclast and B-cell development.
    Genes Dev. 1997 Dec 15;11(24):3482-96 PMID: 9407039
  8. Promiscuous gene expression in thymic epithelial cells is regulated at multiple levels.
    J Exp Med. 2005 Jul 4;202(1):33-45 PMID: 15983066
  9. NF-kappaB2 is required for the control of autoimmunity by regulating the development of medullary thymic epithelial cells.
    J Biol Chem. 2006 Dec 15;281(50):38617-24 PMID: 17046818
  10. Expression of relB is required for the development of thymic medulla and dendritic cells.
    Nature. 1995 Feb 9;373(6514):531-6 PMID: 7845467
  11. Major histocompatibility complex class II-positive cortical epithelium mediates the selection of CD4(+)25(+) immunoregulatory T cells.
    J Exp Med. 2001 Aug 20;194(4):427-38 PMID: 11514600
  12. Peptide-induced negative selection of thymocytes activates transcription of an NF-kappa B inhibitor.
    Mol Cell. 2002 Mar;9(3):637-48 PMID: 11931770
  13. CCR7 directs the migration of thymocytes into the thymic medulla.
    J Immunol. 2004 Apr 1;172(7):3999-4007 PMID: 15034011
  14. Inefficient ZAP-70 phosphorylation and decreased thymic selection in vivo result from inhibition of NF-kappaB/Rel.
    J Immunol. 2001 Nov 15;167(10):5628-35 PMID: 11698434
  15. The impact of negative selection on thymocyte migration in the medulla.
    Nat Immunol. 2009 Aug;10(8):823-30 PMID: 19543275
  16. Expanded nuclear roles for IkappaBs.
    Sci STKE. 2004 Oct 12;2004(254):pe48 PMID: 15479861
  17. Essential role of RelB in germinal center and marginal zone formation and proper expression of homing chemokines.
    J Immunol. 2001 Aug 15;167(4):1909-19 PMID: 11489970
  18. Essential role of IkappaB kinase alpha in thymic organogenesis required for the establishment of self-tolerance.
    J Immunol. 2006 Apr 1;176(7):3995-4002 PMID: 16547234
  19. 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 Nov 15;173(10):6161-8 PMID: 15528353
  20. Characterization of regulatory elements and methylation pattern of the autoimmune regulator (AIRE) promoter.
    J Biol Chem. 2003 May 30;278(22):19784-90 PMID: 12651856
  21. A central role for central tolerance.
    Annu Rev Immunol. 2006;24:571-606 PMID: 16551260
  22. Generation and activation of multiple dimeric transcription factors within the NF-kappaB signaling system.
    Mol Cell Biol. 2008 May;28(10):3139-50 PMID: 18299388
  23. Foxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease.
    Immunol Rev. 2006 Aug;212:8-27 PMID: 16903903
  24. Activation of cortical and inhibited differentiation of medullary epithelial cells in the thymus of lymphotoxin-beta receptor-deficient mice: an ultrastructural study.
    J Anat. 2008 Feb;212(2):114-24 PMID: 18194204
  25. CCR7 signals are essential for cortex-medulla migration of developing thymocytes.
    J Exp Med. 2004 Aug 16;200(4):493-505 PMID: 15302902
  26. Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells.
    Nat Immunol. 2007 Apr;8(4):351-8 PMID: 17322887
  27. The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance.
    Immunity. 2008 Sep 19;29(3):423-37 PMID: 18799149
  28. Lymphotoxin pathway directs thymic Aire expression.
    Nat Immunol. 2003 Nov;4(11):1121-7 PMID: 14517552
  29. 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 Nov;19(11):7688-96 PMID: 10523657
  30. Cutting edge: developmental switches in chemokine responses during T cell maturation.
    J Immunol. 1999 Sep 1;163(5):2353-7 PMID: 10452965
  31. Dependence of self-tolerance on TRAF6-directed development of thymic stroma.
    Science. 2005 Apr 8;308(5719):248-51 PMID: 15705807
  32. Lymphotoxin pathway-directed, autoimmune regulator-independent central tolerance to arthritogenic collagen.
    J Immunol. 2006 Jul 1;177(1):290-7 PMID: 16785524
  33. A role for the IkappaB family member Bcl-3 in the control of central immunologic tolerance.
    Immunity. 2007 Sep;27(3):438-52 PMID: 17869136
  34. Regulation of secondary lymphoid organ development by the nuclear factor-kappaB signal transduction pathway.
    Immunol Rev. 2003 Oct;195:91-105 PMID: 12969313
  35. Thymic medullary epithelial cell differentiation, thymocyte emigration, and the control of autoimmunity require lympho-epithelial cross talk via LTbetaR.
    J Exp Med. 2003 Sep 1;198(5):757-69 PMID: 12953095
  36. NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100.
    Mol Cell. 2001 Feb;7(2):401-9 PMID: 11239468
  37. Circuitry of nuclear factor kappaB signaling.
    Immunol Rev. 2006 Apr;210:171-86 PMID: 16623771
  38. Mature T cells depend on signaling through the IKK complex.
    Immunity. 2003 Sep;19(3):377-89 PMID: 14499113
  39. Differential regulation of CCL21 in lymphoid/nonlymphoid tissues for effectively attracting T cells to peripheral tissues.
    J Clin Invest. 2003 Nov;112(10):1495-505 PMID: 14617751
  40. The cellular mechanism of Aire control of T cell tolerance.
    Immunity. 2005 Aug;23(2):227-39 PMID: 16111640
  41. A fourth IkappaB protein within the NF-kappaB signaling module.
    Cell. 2007 Jan 26;128(2):369-81 PMID: 17254973
  42. Thymic T cell development and progenitor localization depend on CCR7.
    J Exp Med. 2004 Aug 16;200(4):481-91 PMID: 15302903
  43. NF-kappaB2 is required for the establishment of central tolerance through an Aire-dependent pathway.
    J Clin Invest. 2006 Nov;116(11):2964-71 PMID: 17039258
  44. Impaired responsiveness to T-cell receptor stimulation and defective negative selection of thymocytes in CCR7-deficient mice.
    Blood. 2007 Dec 15;110(13):4351-9 PMID: 17785582
  45. Projection of an immunological self shadow within the thymus by the aire protein.
    Science. 2002 Nov 15;298(5597):1395-401 PMID: 12376594
  46. RelB forms transcriptionally inactive complexes with RelA/p65.
    J Biol Chem. 2003 May 30;278(22):19852-60 PMID: 12657634
  47. Multiple nuclear factors interact with the immunoglobulin enhancer sequences.
    Cell. 1986 Aug 29;46(5):705-16 PMID: 3091258
  48. Combined deficiency of p50 and cRel in CD4+ T cells reveals an essential requirement for nuclear factor kappaB in regulating mature T cell survival and in vivo function.
    J Exp Med. 2003 Apr 7;197(7):861-74 PMID: 12668645
  49. NF-kappa B-inducing kinase establishes self-tolerance in a thymic stroma-dependent manner.
    J Immunol. 2004 Feb 15;172(4):2067-75 PMID: 14764671
  50. Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from cells expressing claudin.
    Nat Immunol. 2007 Mar;8(3):304-11 PMID: 17277780
  51. Regulatory T cell lineage specification by the forkhead transcription factor foxp3.
    Immunity. 2005 Mar;22(3):329-41 PMID: 15780990
  52. RelA repression of RelB activity induces selective gene activation downstream of TNF receptors.
    Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14635-40 PMID: 16192349
  53. Regulation of naive T cell function by the NF-kappaB2 pathway.
    Nat Immunol. 2006 Jul;7(7):763-72 PMID: 16732290
  54. The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator.
    Immunity. 2008 Sep 19;29(3):438-50 PMID: 18799150
Article Info
Journal
Cellular & molecular immunology
Abbr.
Cell Mol Immunol
ISSN
2042-0226
DOI
10.1038/cmi.2009.112
Email
zhumz@ibp.ac.cn
Published
2010-03-00
Pages
89-93
Language
English
Region
China
NLM ID
101242872
PMCID
PMC4001888
Subset
IM
External Links
PubMed source DOI: 10.1038/cmi.2009.112 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2