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Journal of Biomedicine and Biotechnology
Volume 2012, Article ID 147413, 5 pages
http://dx.doi.org/10.1155/2012/147413
Review Article

Ustekinumab in Psoriasis Immunopathology with Emphasis on the Th17-IL23 Axis: A Primer

1Department of Dermatopathology, University Hospital of Liège, 4000 Liège, Belgium
2Faculty of Medicine, University of Franche-Comté, 25000 Besançon, France
3Department of Dermatology, University Hospital of Besançon, 25000 Besançon, France
4Inserm Research Unit U645, IFR133, 25000 Besançon, France

Received 31 January 2012; Revised 5 March 2012; Accepted 5 March 2012

Academic Editor: Enzo Berardesca

Copyright © 2012 Pascale Quatresooz et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. G. E. Piérard, C. Piérard-Franchimont, G. Szepetiuk, P. Paquet, and P. Quatresooz, “The therapeutic potential of TNF-α antagonists for skin psoriasis comorbidities,” Expert Opinion on Biological Therapy, vol. 10, no. 8, pp. 1197–1208, 2010. View at Publisher · View at Google Scholar · View at Scopus
  2. B. J. Nickoloff and F. O. Nestle, “Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities,” Journal of Clinical Investigation, vol. 113, no. 12, pp. 1664–1675, 2004. View at Publisher · View at Google Scholar · View at Scopus
  3. C. E. Griffiths and J. N. Barker, “Pathogenesis and clinical features of psoriasis,” The Lancet, vol. 370, no. 9583, pp. 263–271, 2007. View at Publisher · View at Google Scholar · View at Scopus
  4. F. O. Nestle, D. H. Kaplan, and J. Barker, “Mechanisms of disease: psoriasis,” New England Journal of Medicine, vol. 361, no. 5, pp. 444–509, 2009. View at Publisher · View at Google Scholar · View at Scopus
  5. M. Kurzeja, L. Rudnicka, and M. Olszewska, “New interleukin-23 pathway inhibitors in dermatology: ustekinumab, briakinumab, and secukinumab,” American Journal of Clinical Dermatology, vol. 12, no. 2, pp. 113–125, 2011. View at Publisher · View at Google Scholar · View at Scopus
  6. N. Yeilding, P. Szapary, C. Brodmerkel et al., “Development of the IL-12/23 antagonist ustekinumab in psoriasis: past, present, and future perspectives,” Annals of the New York Academy of Sciences, vol. 1222, no. 1, pp. 30–39, 2011. View at Publisher · View at Google Scholar · View at Scopus
  7. B. J. Nickoloff and F. O. Nestle, “Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities,” Journal of Clinical Investigation, vol. 113, no. 12, pp. 1664–1675, 2004. View at Publisher · View at Google Scholar · View at Scopus
  8. A. Menter, A. Gottlieb, S. R. Feldman et al., “Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics,” Journal of the American Academy of Dermatology, vol. 58, no. 5, pp. 826–850, 2008. View at Publisher · View at Google Scholar · View at Scopus
  9. L. Lyakh, G. Trinchieri, L. Provezza, G. Carra, and F. Gerosa, “Regulation of interleukin-12/interleukin-23 production and the T-helper 17 response in humans,” Immunological Reviews, vol. 226, no. 1, pp. 112–131, 2008. View at Publisher · View at Google Scholar · View at Scopus
  10. G. Trinchieri, “Interleukin-12 and the regulation of innate resistance and adaptive immunity,” Nature Reviews Immunology, vol. 3, no. 2, pp. 133–146, 2003. View at Publisher · View at Google Scholar · View at Scopus
  11. B. Oppmann, R. Lesley, B. Blom et al., “Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12,” Immunity, vol. 13, no. 5, pp. 715–725, 2000. View at Google Scholar · View at Scopus
  12. S. Aggarwal, N. Ghilardi, M. H. Xie, F. J. De Sauvage, and A. L. Gurney, “Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17,” Journal of Biological Chemistry, vol. 278, no. 3, pp. 1910–1914, 2003. View at Publisher · View at Google Scholar · View at Scopus
  13. N. J. Wilson, K. Boniface, J. R. Chan et al., “Development, cytokine profile and function of human interleukin 17-producing helper T cells,” Nature Immunology, vol. 8, no. 9, pp. 950–957, 2007. View at Publisher · View at Google Scholar · View at Scopus
  14. D. H. Presky, H. Yang, L. J. Minetti et al., “A functional interleukin 12 receptor complex is composed of two β-type cytokine receptor subunits,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 24, pp. 14002–14007, 1996. View at Google Scholar · View at Scopus
  15. C. Parham, M. Chirica, J. Timans et al., “A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rβ1 and a novel cytokine receptor subunit, IL-23R,” Journal of Immunology, vol. 168, no. 11, pp. 5699–5708, 2002. View at Google Scholar · View at Scopus
  16. L. Yang, D. E. Anderson, C. Baecher-Allan et al., “IL-21 and TGF-β are required for differentiation of human T H17 cells,” Nature, vol. 454, no. 7202, pp. 350–352, 2008. View at Publisher · View at Google Scholar · View at Scopus
  17. F. O. Nestle and C. Conrad, “The IL-12 family member p40 chain as a master switch and novel therapeutic target in psoriasis,” Journal of Investigative Dermatology, vol. 123, no. 6, pp. 14–15, 2004. View at Publisher · View at Google Scholar · View at Scopus
  18. B. J. Nickoloff, “Cracking the cytokine code in psoriasis,” Nature Medicine, vol. 13, no. 3, pp. 242–244, 2007. View at Publisher · View at Google Scholar · View at Scopus
  19. M. A. Lowes, T. Kikuchi, J. Fuentes-Duculan et al., “Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells,” Journal of Investigative Dermatology, vol. 128, no. 5, pp. 1207–1211, 2008. View at Publisher · View at Google Scholar · View at Scopus
  20. G. Piskin, R. M. R. Sylva-Steenland, J. D. Bos, and M. B. M. Teunissen, “In vitro and in situ expression of IL-23 by keratinocytes in healthy skin and psoriasis lesions: enhanced expression in psoriatic skin,” Journal of Immunology, vol. 176, no. 3, pp. 1908–1915, 2006. View at Google Scholar · View at Scopus
  21. D. C. Torti and S. R. Feldman, “Interleukin-12, interleukin-23, and psoriasis: currentprospects,” Journal of the American Academy of Dermatology, vol. 57, no. 6, pp. 1059–1068, 2007. View at Publisher · View at Google Scholar · View at Scopus
  22. A. B. Kimball, K. B. Gordon, R. G. Langley, A. Menter, E. K. Chartash, and J. Valdes, “Safety and efficacy of ABT-874, a fully human interleukin 12/23 monoclonal antibody, in the treatment of moderate to severe chronic plaque psoriasis: results of a randomized, placebo-controlled, phase 2 trial,” Archives of Dermatology, vol. 144, no. 2, pp. 200–207, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. M. Cargill, S. J. Schrodi, M. Chang et al., “A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes,” American Journal of Human Genetics, vol. 80, no. 2, pp. 273–290, 2007. View at Publisher · View at Google Scholar · View at Scopus
  24. R. H. Duerr, K. D. Taylor, S. R. Brant et al., “A genome-wide association study identifies IL23R as an inflammatory bowel disease gene,” Science, vol. 314, no. 5804, pp. 1461–1463, 2006. View at Publisher · View at Google Scholar · View at Scopus
  25. F. Capon, P. Di Meglio, J. Szaub et al., “Sequence variants in the genes for the interleukin-23 receptor (IL23R) and its ligand (IL12B) confer protection against psoriasis,” Human Genetics, vol. 122, no. 2, pp. 201–206, 2007. View at Publisher · View at Google Scholar · View at Scopus
  26. L. C. Zaba, M. Suárez-Fariñas, J. Fuentes-Duculan et al., “Effective treatment of psoriasis with etanercept is linked to suppression of IL-17 signaling, not immediate response TNF genes,” Journal of Allergy and Clinical Immunology, vol. 124, no. 5, pp. 1022–1030, 2009. View at Publisher · View at Google Scholar · View at Scopus
  27. S. M. Sa, P. A. Valdez, J. Wu et al., “The effects of IL-20 subfamily cytokines on reconstituted human epidermis suggest potential roles in cutaneous innate defense and pathogenic adaptive immunity in psoriasis,” Journal of Immunology, vol. 178, no. 4, pp. 2229–2240, 2007. View at Google Scholar · View at Scopus
  28. E. Toichi, G. Torres, T. S. McCormick et al., “An anti-IL-12p40 antibody down-regulates type 1 cytokines, chemokines, and IL-12/IL-23 in psoriasis,” Journal of Immunology, vol. 177, no. 7, pp. 4917–4926, 2006. View at Google Scholar · View at Scopus
  29. M. Jinushi and H. Tahara, “Cytokine gene-mediated immunotherapy: current status and future perspectives,” Cancer Science, vol. 100, no. 8, pp. 1389–1396, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. M. N. Alonso, M. T. Wong, A. L. Zhang et al., “T(H)1, T(H)2, and T(H)17 cells instruct monocytes to differentiate into specialized dendritic cell subsets,” Blood, vol. 118, pp. 3311–3320, 2011. View at Google Scholar
  31. M. A. Lowes, T. Kikuchi, J. Fuentes-Duculan et al., “Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells,” Journal of Investigative Dermatology, vol. 128, no. 5, pp. 1207–1211, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. Z. Yao, S. L. Painter, W. C. Fanslow et al., “Human IL-17: a novel cytokine derived from T cells,” Journal of Immunology, vol. 155, no. 12, pp. 5483–5486, 1995. View at Google Scholar · View at Scopus
  33. K. E. Nograles, L. C. Zaba, E. Guttman-Yassky et al., “Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways,” British Journal of Dermatology, vol. 159, no. 5, pp. 1092–1102, 2008. View at Publisher · View at Google Scholar · View at Scopus
  34. K. E. Nograles, B. Davidovici, and J. G. Krueger, “New Insights in the Immunologic Basis of Psoriasis,” Seminars in Cutaneous Medicine and Surgery, vol. 29, no. 1, pp. 3–9, 2010. View at Publisher · View at Google Scholar · View at Scopus
  35. T. Duhen, R. Geiger, D. Jarrossay, A. Lanzavecchia, and F. Sallusto, “Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells,” Nature Immunology, vol. 10, no. 8, pp. 857–863, 2009. View at Publisher · View at Google Scholar · View at Scopus
  36. S. Trifari, C. D. Kaplan, E. H. Tran, N. K. Crellin, and H. Spits, “Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from TH-17, TH1 and TH2 cells,” Nature Immunology, vol. 10, no. 8, pp. 864–871, 2009. View at Publisher · View at Google Scholar · View at Scopus
  37. N. Yawalkar, S. Karlen, R. Hunger, C. U. Brand, and L. R. Braathen, “Expression of interleukin-12 is increased in psoriatic skin,” Journal of Investigative Dermatology, vol. 111, no. 6, pp. 1053–1057, 1998. View at Publisher · View at Google Scholar · View at Scopus
  38. E. Lee, W. L. Trepicchio, J. L. Oestreicher et al., “Increased Expression of Interleukin 23 p19 and p40 in Lesional Skin of Patients with Psoriasis Vulgaris,” Journal of Experimental Medicine, vol. 199, no. 1, pp. 125–130, 2004. View at Publisher · View at Google Scholar · View at Scopus
  39. S. Aggarwal, N. Ghilardi, M. H. Xie, F. J. De Sauvage, and A. L. Gurney, “Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17,” Journal of Biological Chemistry, vol. 278, no. 3, pp. 1910–1914, 2003. View at Publisher · View at Google Scholar · View at Scopus
  40. G. Piskin, R. M. R. Sylva-Steenland, J. D. Bos, and M. B. M. Teunissen, “In vitro and in situ expression of IL-23 by keratinocytes in healthy skin and psoriasis lesions: enhanced expression in psoriatic skin,” Journal of Immunology, vol. 176, no. 3, pp. 1908–1915, 2006. View at Google Scholar · View at Scopus
  41. N. Yawalkar, G. G. Tscharner, R. E. Hunger, and A. S. Hassan, “Increased expression of IL-12p70 and IL-23 by multiple dendritic cell and macrophage subsets in plaque psoriasis,” Journal of Dermatological Science, vol. 54, no. 2, pp. 99–105, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. J. Luo, S. J. Wu, E. R. Lacy et al., “Structural Basis for the Dual Recognition of IL-12 and IL-23 by Ustekinumab,” Journal of Molecular Biology, vol. 402, no. 5, pp. 797–812, 2010. View at Publisher · View at Google Scholar · View at Scopus
  43. J. D. Croxtall, “Ustekinumab. A review of its use in the management of moderate to severe plaque psoriasis,” Drugs, vol. 71, pp. 1733–1753, 2011. View at Google Scholar
  44. C. L. Kauffman, N. Aria, E. Toichi et al., “A phase I study evaluating the safety, pharmacokinetics, and clinical response of a human IL-12 p40 antibody in subjects with plaque psoriasis,” Journal of Investigative Dermatology, vol. 123, no. 6, pp. 1037–1044, 2004. View at Publisher · View at Google Scholar · View at Scopus
  45. C. L. Leonardi, A. B. Kimball, K. A. Papp et al., “Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76 week results from a randomized, double-blind, placebo-controlled trial (Phoenix 1),” The Lancet, vol. 371, pp. 1665–1674, 2008. View at Google Scholar
  46. E. Rallis, S. Kintzoglou, and C. Verros, “Ustekinumab for rapid treatment of nail psoriasis,” Archives of Dermatology, vol. 146, no. 11, pp. 1315–1316, 2010. View at Publisher · View at Google Scholar · View at Scopus
  47. P. R. Mangan, L. E. Harrington, D. B. O'Quinn et al., “Transforming growth factor-β induces development of the T H17 lineage,” Nature, vol. 441, no. 7090, pp. 231–234, 2006. View at Publisher · View at Google Scholar · View at Scopus
  48. E. Bettelli, Y. Carrier, W. Gao et al., “Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells,” Nature, vol. 441, no. 7090, pp. 235–238, 2006. View at Publisher · View at Google Scholar · View at Scopus
  49. B. S. McKenzie, R. A. Kastelein, and D. J. Cua, “Understanding the IL-23-IL-17 immune pathway,” Trends in Immunology, vol. 27, no. 1, pp. 17–23, 2006. View at Publisher · View at Google Scholar · View at Scopus
  50. M. A. Lowes, A. M. Bowcock, and J. G. Krueger, “Pathogenesis and therapy of psoriasis,” Nature, vol. 445, no. 7130, pp. 866–873, 2007. View at Publisher · View at Google Scholar · View at Scopus
  51. Z. Chen and J. J. O'Shea, “Th17 cells: a new fate for differentiating helper T cells,” Immunologic Research, vol. 41, no. 2, pp. 87–102, 2008. View at Publisher · View at Google Scholar · View at Scopus
  52. K. Kikly, L. Liu, S. Na, and J. D. Sedgwick, “The IL-23/Th17 axis: therapeutic targets for autoimmune inflammation,” Current Opinion in Immunology, vol. 18, no. 6, pp. 670–675, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. A. Asarch, O. Barak, D. S. Loo, and A. B. Gottlieb, “Th17 cells: a new therapeutic target in inflammatory dermatoses,” Journal of Dermatological Treatment, vol. 19, no. 6, pp. 318–326, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. A. Asarch, O. Barak, D. S. Loo, and A. B. Gottlieb, “Th17 cells: a new paradigm for cutaneous inflammation,” Journal of Dermatological Treatment, vol. 19, no. 5, pp. 259–266, 2008. View at Publisher · View at Google Scholar · View at Scopus
  55. K. Komura, M. Fujimoto, M. Hasegawa et al., “Increased serum interleukin 23 in patients with systemic sclerosis,” Journal of Rheumatology, vol. 35, no. 1, pp. 120–125, 2008. View at Google Scholar · View at Scopus
  56. J. M. Larsen, C. M. Bonefeld, S. S. Poulsen, C. Geisler, and L. Skov, “IL-23 and TH17-mediated inflammation in human allergic contact dermatitis,” Journal of Allergy and Clinical Immunology, vol. 123, no. 2, pp. 486–492, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. Y. Zhao, A. Balato, R. Fishelevich, A. Chapoval, D. L. Mann, and A. A. Gaspari, “Th17/Tc17 infiltration and associated cytokine gene expression in elicitation phase of allergic contact dermatitis,” British Journal of Dermatology, vol. 161, no. 6, pp. 1301–1306, 2009. View at Publisher · View at Google Scholar · View at Scopus
  58. C. Ryan, B. Thrash, R. B. Warren, and A. Menter, “The use of ustekinumab in autoimmune disease,” Expert Opinion on Biological Therapy, vol. 10, no. 4, pp. 587–604, 2010. View at Publisher · View at Google Scholar · View at Scopus
  59. C. K. Wong, L. C. W. Lit, L. S. Tam, E. K. M. Li, P. T. Y. Wong, and C. W. K. Lam, “Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity,” Clinical Immunology, vol. 127, no. 3, pp. 385–393, 2008. View at Publisher · View at Google Scholar · View at Scopus
  60. K. Shah, W. W. Lee, S. H. Lee et al., “Dysregulated balance of Th17 and Th1 cells in systemic lupus erythematosus,” Arthritis Research and Therapy, vol. 12, no. 2, article R53, 2010. View at Publisher · View at Google Scholar · View at Scopus
  61. H. R. Kim, H. S. Kim, M. K. Park, M. L. Cho, S. H. Lee, and H. Y. Kim, “The clinical role of IL-23p19 in patients with rheumatoid arthritis,” Scandinavian Journal of Rheumatology, vol. 36, no. 4, pp. 259–264, 2007. View at Publisher · View at Google Scholar · View at Scopus
  62. C. Schmidt, T. Giese, B. Ludwig et al., “Expression of interleukin-12-related cytokine transcripts in inflammatory bowel disease: elevated interleukin-23p19 and interleukin-27p28 in Crohn's disease but not in ulcerative colitis,” Inflammatory Bowel Diseases, vol. 11, no. 1, pp. 16–23, 2005. View at Publisher · View at Google Scholar · View at Scopus
  63. W. Lew, J. Y. Chang, J. Y. Jung, and D. Bang, “Increased expression of interleukin-23 p19 mRNA in erythema nodosum-like lesions of Behçet's disease,” British Journal of Dermatology, vol. 158, no. 3, pp. 505–511, 2008. View at Publisher · View at Google Scholar · View at Scopus