Dendritic Cell: T-Cell Interactions in Spondyloarthritis

  • J. S. Hill Gaston
  • Lorna B. Jarvis
  • Libin Zhang
  • Jane C. Goodall
Part of the Advances in Experimental Medicine and Biology book series (volume 649)


The discovery of the association between spondyloarthritis (SpA) and HLA-B27 inevitably turned the spotlight on T-lymphocytes as the cells which recognize peptide antigens within the binding groove of the HLA-B27 molecule and then carry out effector functions. These include cytolysis, cytokine and chemokine production and activation of other effector cells, such as those which could destroy joints or drive new bone formation. In this view the T-cell assumed the role of “director” of the immune response and therefore, in inflammatory diseases such as SpA, of immuno-pathology. The important research questions under this paradigm were the identity of the peptides recognized by T-cells in disease, including whether they were derived from self proteins or from micro-organisms, the influence of HLA-B27 in selecting antigenic peptides for recognition by T-cells, the T-cell receptors used in recognition and the effector programmes which the T-cells initiated. Whilst these questions continue to be explored—many have not yet been answered—attention has shifted to a new “master regulator” of the immune response, namely the dendritic cell and the possibility that the genetic influences which contribute to susceptibility to SpA do so at the level of the dendritic cell (DC).


Dendritic Cell U937 Cell Unfold Protein Response Pattern Recognition Receptor Unfold Protein Response Activation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Mellman I, Steinman RM. Dendritic cells: Specialized and regulated antigen processing machines. Cell 2001; 106(3):255–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Liu YJ. Dendritic cell subsets and lineages and their functions in innate and adaptive immunity. Cell 2001; 106(3):259–62.PubMedCrossRefGoogle Scholar
  3. 3.
    Takeda K, Kaisho T, Akira S. Toll-like receptors. Annu Rev Immunol 2003; 21:335–76.PubMedCrossRefGoogle Scholar
  4. 4.
    Fritz JH, Ferrero RL, Philpott DJ et al. Nod-like proteins in immunity, inflammation and disease. Nature Immunology 2006; 7(12):1250–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Petrilli V, Dostert C, Muruve DA et al. The inflammasome: a danger sensing complex triggering innate immunity. Curr Opin Immunol 2007; 19(6):615–22.PubMedCrossRefGoogle Scholar
  6. 6.
    Tsan MF, Gao B. Endogenous ligands of Toll-like receptors. J Leukoc Biol 2004; 76(3):514–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Martinon F, Petrilli V, Mayor A et al. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 2006; 440(7081):237–41.PubMedCrossRefGoogle Scholar
  8. 8.
    Hunter CA. New IL-12-family members: IL-23 and IL-27, cytokines with divergent functions. Nat Rev Immunol 2005; 5(7):521–31.PubMedCrossRefGoogle Scholar
  9. 9.
    McGovern DP, van Heel DA, Ahmad T et al. NOD2 (CARD15), the first susceptibility gene for Crohn’s disease. Gut 2001; 49(6):752–4.PubMedCrossRefGoogle Scholar
  10. 10.
    Cargill M, Schrodi SJ, Chang M et al. A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet 2007; 80(2):273–90.PubMedCrossRefGoogle Scholar
  11. 11.
    Duerr RH, Taylor KD, Brant SR et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 2006; 314(5804):1461–3.PubMedCrossRefGoogle Scholar
  12. 13.
    Colbert RA. HLA-B27 misfolding: A solution to the spondyloarthropathy conundrum? Mol Med Today 2000; 6(6):224–30.PubMedCrossRefGoogle Scholar
  13. 14.
    Matyszak MK, Gaston JSH. Chlamydia trachomatis-specific human CD8(+) T-cells show two patterns of antigen recognition. Infect Immun 2004; 72(8):4357–67.PubMedCrossRefGoogle Scholar
  14. 15.
    Jarvis LB, Matyszak MK, Duggleby RC et al. Autoreactive human peripheral blood CD8(+) T-cells with a regulatory phenotype and function. Eur J Immunol 2005; 35(10):2896–908.PubMedCrossRefGoogle Scholar
  15. 16.
    Fontenot JD, Rasmussen JP, Williams LM et al. Regulatory T-cell lineage specification by the forkhead transcription factor foxp3. Immunity 2005; 22(3):329–41.PubMedCrossRefGoogle Scholar
  16. 17.
    Wan YY, Flavell RA. Identifying Foxp3-expressing suppressor T-cells with a bicistronic reporter. Proc Natl Acad Sci USA 2005; 102(14):5126–31.PubMedCrossRefGoogle Scholar
  17. 18.
    Brosterhus H, Brings S, Leyendeckers H et al. Enrichment and detection of live antigen-specific CD4(+) and CD8(+) T-cells based on cytokine secretion. Eur J Immunol 1999; 29(12):4053–9.PubMedCrossRefGoogle Scholar
  18. 19.
    Valk E, Leung R, Kang H et al. T-cell receptor-interacting molecule acts as a chaperone to modulate surface expression of the CTLA-4 coreceptor. Immunity 2006; 25(5):807–21.PubMedCrossRefGoogle Scholar
  19. 20.
    Gavin MA, Torgerson TR, Houston E et al. Single-cell analysis of normal and FOXP3-mutant human T-cells: FOXP3 expression without regulatory T-cell development. Proc Natl Acad Sci USA. 2006; 103(17):6659–64.PubMedCrossRefGoogle Scholar
  20. 21.
    Xystrakis E, Dejean AS, Bernard I et al. Identification of a novel natural regulatory CD8 T-cell subset and analysis of its mechanism of regulation. Blood 2004; 104(10):3294–301.PubMedCrossRefGoogle Scholar
  21. 22.
    Taurog JD, Richardson JA, Croft JT et al. The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J Exp Med 1994; 180(6):2359–64.PubMedCrossRefGoogle Scholar
  22. 23.
    Turner MJ, Sowders DP, DeLay ML et al. HLA-B27 misfolding in transgenic rats is associated with activation of the unfolded protein response. J Immunol 2005; 175(4):2438–48.PubMedGoogle Scholar
  23. 24.
    Goodall JC, Ellis L, Yeo GS et al. Does HLA-B27 influence the monocyte inflammatory response to lipopolysaccharide? Rheumatology (Oxford) 2007; 46(2):232–7.CrossRefGoogle Scholar
  24. 25.
    Mise-Omata S, Kuroda E, Niikura J et al. A proximal kappaB site in the IL-23 p19 promoter is responsible for RelA-and c-Rel-dependent transcription. J Immunol 2007; 179(10):6596–603.PubMedGoogle Scholar
  25. 26.
    Utsugi M, Dobashi K, Ishizuka T et al. Rac1 negatively regulates lipopolysaccharide-induced IL-23 p19 expression in human macrophages and dendritic cells and NF-kappaB p65 trans activation plays a novel role. J Immunol 2006; 177(7):4550–7.PubMedGoogle Scholar
  26. 27.
    McKenzie BS, Kastelein RA, Cua DJ. Understanding the IL-23-IL-17 immune pathway. Trends Immunol 2006; 27(1):17–23.PubMedCrossRefGoogle Scholar
  27. 28.
    Tada H, Aiba S, Shibata K et al. Synergistic effect of Nod1 and Nod2 agonists with toll-like receptor agonists on human dendritic cells to generate interleukin-12 and T helper type 1 cells. Infect Immun 2005; 73(12):7967–76.PubMedCrossRefGoogle Scholar
  28. 29.
    Yang CS, Song CH, Lee JS et al. Intracellular network of phosphatidylinositol 3-kinase, mammalian target of the rapamycin/70 kDa ribosomal S6 kinase 1 and mitogen-activated protein kinases pathways for regulating mycobacteria-induced IL-23 expression in human macrophages. Cell Microbiol 2006; 8(7):1158–71.PubMedCrossRefGoogle Scholar
  29. 30.
    LeibundGut Landmann S, Gross O, Robinson MJ et al. Syk-and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nat Immunol 2007; 8(6):630–8.CrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2009

Authors and Affiliations

  • J. S. Hill Gaston
    • 1
  • Lorna B. Jarvis
    • 1
  • Libin Zhang
    • 1
  • Jane C. Goodall
    • 1
  1. 1.Department of RheumatologyUniversity of Cambridge Addenbrooke’s HospitalCambridgeUK

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