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Dendritic cells in the pathogenesis of ankylosing spondylitis and axial spondyloarthritis

  • Gleb Slobodin
  • Itzhak Rosner
  • Aharon Kessel
Review Article

Abstract

The interaction of dendritic cells (DCs) with the human microbiome, with distorted handling of the microbiota or its products via the direct effect of HLA B27, probably represents the initial element in the chain of events leading to the development of clinical axial spondyloarthritis. The mechanism of disease extension onto the skeleton and other tissues involved, such as uvea, may also involve migratory DCs. Finally, the role of DCs in the initiation of the inflammatory tissue response with activation of the IL-17 axis has been demonstrated. Further, some initial data suggests the possible connection of DCs with disease-related new bone formation.

Keywords

Ankylosing spondylitis Axial spondyloarthritis Dendritic cells 

Notes

Compliance with ethical standards

Disclosures

None.

References

  1. 1.
    Taurog JD, Chhabra A, Colbert RA (2016) Ankylosing spondylitis and axial spondyloarthritis. N Engl J Med Jun 374(26):2563–2574CrossRefGoogle Scholar
  2. 2.
    Robinson PC, Brown MA (2014) Genetics of ankylosing spondylitis. Mol Immunol Jan 57(1):2–11CrossRefGoogle Scholar
  3. 3.
    Powis SJ, Colbert RA (2016) Editorial: HLA-B27: the story continues to unfold. Arthritis Rheumatol. 68(5):1057–1059PubMedPubMedCentralGoogle Scholar
  4. 4.
    Breban M, Tap J, Leboime A, Said-Nahal R, Langella P, Chiocchia G, Furet JP, Sokol H (2017) Faecal microbiota study reveals specific dysbiosis in spondyloarthritis. Ann Rheum Dis 76(9):1614–1622CrossRefPubMedGoogle Scholar
  5. 5.
    Wen C, Zheng Z, Shao T, Liu L, Xie Z, Le Chatelier E, He Z, Zhong W, Fan Y, Zhang L, Li H, Wu C, Hu C, Xu Q, Zhou J, Cai S, Wang D, Huang Y, Breban M, Qin N, Ehrlich SD (2017) Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis. Genome Biol 18(1):142CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Gill T, Asquith M, Rosenbaum JT, Colbert RA (2015) The intestinal microbiome in spondyloarthritis. Curr Opin Rheumatol 27(4):319–325CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Asquith M, Davin S, Stauffer P, Michell C, Janowitz C, Lin P, Ensign-Lewis J, Kinchen JM, Koop DR, Rosenbaum JT (2017) Intestinal metabolites are profoundly altered in the context of HLA-B27 expression and functionally modulate disease in a rat model of spondyloarthritis. Arthritis Rheumatol 69(10):1984–1995CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Smolinska S, Groeger D, O'Mahony L (2017) Biology of the microbiome 1: interactions with the host immune response. Gastroenterol Clin N Am 46(1):19–35CrossRefGoogle Scholar
  9. 9.
    Krajewska-Wlodarczyk M, Owczarczyk-Saczonek A, Placek W, Osowski A, Engelgardt P, Wojtkiewicz J (2017) Role of stem cells in pathophysiology and therapy of spondyloarthropathies-new therapeutic possibilities? Int J Mol Sci 28(19):1Google Scholar
  10. 10.
    Pepelyayeva Y, Rastall DPW, Aldhamen YA, O’Connell P, Raehtz S, Alyaqoub Blake MK, Raedy AM, Angarita AM, Abbas AM, Pereira-Hicks CN, Roosa SG, McCabe L, Amalfitano A (2018) ERAP1 deficient mice have reduced type 1 regulatory T cells and develop skeletal and intestinal features of ankylosing spondylitis. Sci Rep 8(1):12464CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Berthelot JM, Claudepierre P (2016) Trafficking of antigens from gut to sacroiliac joints and spine in reactive arthritis and spondyloarthropathies: mainly through lymphatics? Joint Bone Spine 83(5):485–490CrossRefPubMedGoogle Scholar
  12. 12.
    Hacquard-Bouder C, Falgarone G, Bosquet A, Smaoui F, Monnet D, Ittah M, Breban M (2004) Defective costimulatory function is a striking feature of antigen-presenting cells in an HLA-B27-transgenic rat model of spondyloarthropathy. Arthritis Rheum 50(5):1624–1635CrossRefPubMedGoogle Scholar
  13. 13.
    Hacquard-Bouder C, Chimenti MS, Giquel B, Donnadieu E, Fert I, Schmitt A, André C, Breban M (2007) Alteration of antigen-independent immunologic synapse formation between dendritic cells from HLA-B27-transgenic rats and CD4+ T cells: selective impairment of costimulatory molecule engagement by mature HLA- B27. Arthritis Rheum 56(5):1478–1489CrossRefPubMedGoogle Scholar
  14. 14.
    Dhaenens M, Fert I, Glatigny S, Haerinck S, Poulain C, Donnadieu E, Hacquard-Bouder C, Andre C, Elewaut D, Deforce D, Breban M (2009) Dendritic cells from spondyloarthritis-prone HLA-B27-transgenic rats display altered cytoskeletal dynamics, class II major histocompatibility complex expression, and viability. Arthritis Rheum 60(9):2622–2632CrossRefPubMedGoogle Scholar
  15. 15.
    Slobodin G, Kessel A, Kofman N, Toubi E, Rosner I, Odeh M (2012) Phenotype of resting and activated monocyte-derived dendritic cells grown from peripheral blood of patients with ankylosing spondylitis. Inflammation 35(2):772–775CrossRefPubMedGoogle Scholar
  16. 16.
    Fert I, Glatigny S, Poulain C, Satumtira N, Dorris ML, Taurog JD, Breban M (2008) Correlation between dendritic cell functional defect and spondyloarthritis phenotypes in HLA-B27/HUMAN beta2-microglobulin-transgenic rat lines. Arthritis Rheum 58(11):3425–3429CrossRefPubMedGoogle Scholar
  17. 17.
    Talpin A, Costantino F, Bonilla N, Leboime A, Letourneur F, Jacques S, Dumont F, Amraoui S, Dutertre CA, Garchon HJ, Breban M, Chiocchia G (2014) Monocyte- derived dendritic cells from HLA-B27+ axial spondyloarthritis (SpA) patients display altered functional capacity and deregulated gene expression. Arthritis Res Ther. 16(4):417CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Utriainen L, Firmin D, Wright P, Cerovic V, Breban M, McInnes I, Milling S (2012) Expression of HLA-B27 causes loss of migratory dendritic cells in a rat model of spondyloarthritis. Arthritis Rheum 64(10):3199–3209CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Fert I, Cagnard N, Glatigny S, Letourneur F, Jacques S, Smith JA, Colbert RA, Taurog JD, Chiocchia G, Araujo LM, Breban M (2014) Reverse interferon signature is characteristic of antigen-presenting cells in human and rat spondyloarthritis. Arthritis Rheumatol. 66(4):841–851CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Santos SG, Lynch S, Campbell EC, Antoniou AN, Powis SJ (2008) Induction of HLA- B27 heavy chain homodimer formation after activation in dendritic cells. Arthritis Res Ther 10(4):R100CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Raine T, Brown D, Bowness P, Hill Gaston JS, Moffett A, Trowsdale J, Allen RL (2006) Consistent patterns of expression of HLA class I free heavy chains in healthy individuals and raised expression in spondyloarthropathy patients point to physiological and pathological roles. Rheumatology (Oxford) 45(11):1338–1344CrossRefGoogle Scholar
  22. 22.
    Wong-Baeza I, Ridley A, Shaw J, Hatano H, Rysnik O, McHugh K, Piper C, Brackenbridge S, Fernandes R, Chan A, Bowness P, Kollnberger S (2013) KIR3DL2 binds to HLA-B27 dimers and free H chains more strongly than other HLA class I and promotes the expansion of T cells in ankylosing spondylitis. J Immunol 190(7):3216–3224CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Wright PB, McEntegart A, McCarey D, McInnes IB, Siebert S, Milling SW (2016) Ankylosing spondylitis patients display altered dendritic cell and T cell populations that implicate pathogenic roles for the IL-23 cytokine axis and intestinal inflammation. Rheumatology (Oxford) 55(1):120–132CrossRefGoogle Scholar
  24. 24.
    Pang L, Wang L, Suo T, Hao H, Fang X, Jia J, Huang F, Tang J (2008) Tumor necrosis factor-alpha blockade leads to decreased peripheral T cell reactivity and increased dendritic cell number in peripheral blood of patients with ankylosing spondylitis. J Rheumatol 35(11):2220–2228CrossRefPubMedGoogle Scholar
  25. 25.
    Hallett RM, Chew T (2014) Immune cell transcript modules reveal leukocyte heterogeneity in synovial biopsies of seronegative spondyloarthropathy patients. BMC Musculoskelet Disord 15:446CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Appel H, Maier R, Bleil J, Hempfing A, Loddenkemper C, Schlichting U, Syrbe U, Sieper J (2013) In situ analysis of interleukin-23- and interleukin-12-positive cells in the spine of patients with ankylosing spondylitis. Arthritis Rheum 65(6):1522–1529CrossRefPubMedGoogle Scholar
  27. 27.
    Glatigny S, Fert I, Blaton MA, Lories RJ, Araujo LM, Chiocchia G, Breban M (2012) Proinflammatory Th17 cells are expanded and induced by dendritic cells in spondyloarthritis-prone HLA-B27-transgenic rats. Arthritis Rheum 64(1):110–120CrossRefPubMedGoogle Scholar
  28. 28.
    Smith JA, Barnes MD, Hong D, DeLay ML, Inman RD, Colbert RA (2008) Gene expression analysis of macrophages derived from ankylosing spondylitis patients reveals interferon-gamma dysregulation. Arthritis Rheum 58(6):1640–1649CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Cortes A, Maksymowych WP, Wordsworth BP, Inman RD, Danoy P, Rahman P, Stone MA, Corr M, Gensler LS, Gladman D, Morgan A, Marzo-Ortega H, Ward MM, SPARCC (Spondyloarthritis Research Consortium of Canada); TASC (Australo-Anglo-American Spondyloarthritis Consortium), Learch TJ, Reveille JD, Brown MA, Weisman MH (2015) Association study of genes related to bone formation and resorption and the extent of radiographic change in ankylosing spondylitis. Ann Rheum Dis 74(7):1387–1393CrossRefPubMedGoogle Scholar
  30. 30.
    Collin M, Bigley V (2018) Human dendritic cell subsets: an update. Immunology 154(1):3–20CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Tiberio L, Del Prete A, Schioppa T, Sozio F, Bosisio D, Sozzani S (2018) Chemokine and chemotactic signals in dendritic cell migration. Cell Mol Immunol 15:346–352.  https://doi.org/10.1038/s41423-018-0005-3 CrossRefPubMedGoogle Scholar
  32. 32.
    Clark GJ, Silveira PA, Hogarth PM, Hart DNJ (2018) The cell surface phenotype of human dendritic cells. Semin Cell Dev Biol pii S1084-9521(17):30494–30499Google Scholar
  33. 33.
    Domogalla MP, Rostan PV, Raker VK, Steinbrink K (2017) Tolerance through education: how tolerogenic dendritic cells shape immunity. Front Immunol 8:1764CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2018

Authors and Affiliations

  1. 1.Rheumatology UnitBnai Zion Medical CenterHaifaIsrael
  2. 2.Ruth and Bruce Rappaport Faculty of MedicineTechnionHaifaIsrael
  3. 3.Division of Allergy and Clinical ImmunologyBnai Zion Medical CenterHaifaIsrael

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