Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Pathogenesis and therapy of psoriasis

Nature volume 445, pages 866–873 (2007)Cite this article

Abstract

Psoriasis is one of the most common human skin diseases and is considered to have key genetic underpinnings. It is characterized by excessive growth and aberrant differentiation of keratinocytes, but is fully reversible with appropriate therapy. The trigger of the keratinocyte response is thought to be activation of the cellular immune system, with T cells, dendritic cells and various immune-related cytokines and chemokines implicated in pathogenesis. The newest therapies for psoriasis target its immune components and may predict potential treatments for other inflammatory human diseases.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Histological components of a mature psoriatic plaque compared with normal skin.
Figure 2: A dynamic picture of the bidirectional flow of 'information' and cells in a mature psoriasis lesion: the yin and yang of psoriasis.
Figure 3: Potential cytokine networks in psoriatic lesions.
Figure 4: Effective treatments are available for psoriasis and reverse the disease phenotype.

Similar content being viewed by others

References

  1. Krueger, J. G. The immunologic basis for the treatment of psoriasis with new biologic agents. J. Am. Acad. Dermatol. 46, 1–23 (2002).

    Article  Google Scholar 

  2. Lebwohl, M. Psoriasis. Lancet 361, 1197–1204 (2003).

    Article  Google Scholar 

  3. Nickoloff, B. J. & Nestle, F. O. Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities. J. Clin. Invest. 113, 1664–1675 (2004).

    Article  CAS  Google Scholar 

  4. Bowcock, A. M. & Krueger, J. G. Getting under the skin: the immunogenetics of psoriasis. Nature Rev. Immunol. 5, 699–711 (2005).

    Article  CAS  Google Scholar 

  5. Schon, M. P. & Boehncke, W. H. Psoriasis. N. Engl. J. Med. 352, 1899–1912 (2005).

    Article  CAS  Google Scholar 

  6. Gaspari, A. A. Innate and adaptive immunity and the pathophysiology of psoriasis. J. Am. Acad. Dermatol. 54, S67–S80 (2006).

    Article  Google Scholar 

  7. Davidson, A. & Diamond, B. Autoimmune diseases. N. Engl. J. Med. 345, 340–350 (2001).

    Article  CAS  Google Scholar 

  8. Liu, Y., Krueger, J. G. & Bowcock, A. M. Psoriasis: genetic associations and immune system changes. Genes Immunity advance online publication (9 November 2006) doi:10.1038/sj.gene.6364351.

    Article  CAS  Google Scholar 

  9. Christensen, T. E. et al. Observations of psoriasis in the absence of therapeutic intervention identifies two unappreciated morphologic variants, thin-plaque and thick-plaque psoriasis, and their associated phenotypes. J. Invest. Dermatol. 126, 2397–2403 (2006).

    Article  CAS  Google Scholar 

  10. Lew, W., Lee, E. & Krueger, J. G. Psoriasis genomics: analysis of proinflammatory (type 1) gene expression in large plaque (Western) and small plaque (Asian) psoriasis vulgaris. Br. J. Dermatol. 150, 668–676 (2004).

    Article  CAS  Google Scholar 

  11. Clark, R. A. et al. The vast majority of CLA+ T cells are resident in normal skin. J. Immunol. 176, 4431–4439 (2006).

    Article  CAS  Google Scholar 

  12. Boyman, O. et al. Activation of dendritic antigen-presenting cells expressing common heat shock protein receptor CD91 during induction of psoriasis. Br. J. Dermatol. 152, 1211–1218 (2005).

    Article  CAS  Google Scholar 

  13. Boyman, O. et al. Spontaneous development of psoriasis in a new animal model shows an essential role for resident T cells and tumor necrosis factor-α. J. Exp. Med. 199, 731–736 (2004).

    Article  CAS  Google Scholar 

  14. Lew, W., Bowcock, A. M. & Krueger, J. G. Psoriasis vulgaris: cutaneous lymphoid tissue supports T-cell activation and 'Type 1' inflammatory gene expression. Trends Immunol. 25, 295–305 (2004).

    Article  CAS  Google Scholar 

  15. Nestle, F. O. et al. Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production. J. Exp. Med. 202, 135–143 (2005).

    Article  CAS  Google Scholar 

  16. Lowes, M. A. et al. Increase in TNF-α and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a). Proc. Natl Acad. Sci. USA 102, 19057–19062 (2005).

    Article  ADS  CAS  Google Scholar 

  17. Larrengina, A. T. & Falo, L. D. Changing paradigms in cutaneous immunology: adapting with dendritic cells. J. Invest. Dermatol. 124, 1–12 (2005).

    Article  Google Scholar 

  18. Serbina, N. V., Salazar-Mather, T. P., Biron, C. A., Kuziel, W. A. & Pamer, E. G. TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection. Immunity 19, 59–70 (2003).

    Article  CAS  Google Scholar 

  19. Lee, E. et al. Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. J. Exp. Med. 199, 125–130 (2004).

    Article  CAS  Google Scholar 

  20. Wang, F. et al. Prominent production of IL-20 by CD68+/CD11c+ myeloid-derived cells in psoriasis: gene regulation and cellular effects. J. Invest. Dermatol. 126, 1590–1599 (2006).

    Article  CAS  Google Scholar 

  21. Zhou, X. et al. Novel mechanisms of T-cell and dendritic cell activation revealed by profiling of psoriasis on the 63,100-element oligonucleotide array. Physiol. Genomics 13, 69–78 (2003).

    Article  CAS  Google Scholar 

  22. Weninger, W. et al. Naive T cell recruitment to nonlymphoid tissues: a role for endothelium-expressed CC chemokine ligand 21 in autoimmune disease and lymphoid neogenesis. J. Immunol. 170, 4638–4648 (2003).

    Article  CAS  Google Scholar 

  23. Weninger, W. & von Andrian, U. H. Chemokine regulation of naive T cell traffic in health and disease. Semin. Immunol. 15, 257–270 (2003).

    Article  CAS  Google Scholar 

  24. McKenzie, B. S., Kastelein, R. A. & Cua, D. J. Understanding the IL-23–IL-17 immune pathway. Trends Immunol. 27, 17–23 (2006).

    Article  CAS  Google Scholar 

  25. Nickoloff, B. J., Bonish, B., Huang, B. B. & Porcelli, S. A. Characterization of a T cell line bearing natural killer receptors and capable of creating psoriasis in a SCID mouse model system. J. Dermatol. Sci. 24, 212–225 (2000).

    Article  CAS  Google Scholar 

  26. Prinz, J. C. et al. T cell clones from psoriasis skin lesions can promote keratinocyte proliferation in vitro via secreted products. Eur. J. Immunol. 24, 593–598 (1994).

    Article  CAS  Google Scholar 

  27. Sugiyama, H. et al. Dysfunctional blood and target tissue CD4+CD25high regulatory T cells in psoriasis: mechanism underlying unrestrained pathogenic effector T cell proliferation. J. Immunol. 174, 164–173 (2005).

    Article  CAS  Google Scholar 

  28. Gottlieb, S. L. et al. Response of psoriasis to a lymphocyte-selective toxin (DAB389IL-2) suggests a primary immune, but not keratinocyte, pathogenic basis. Nature Med. 1, 442–447 (1995).

    Article  CAS  Google Scholar 

  29. Abrams, J. R. et al. CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris. J. Clin. Invest. 103, 1243–1252 (1999).

    Article  CAS  Google Scholar 

  30. Abrams, J. R. et al. Blockade of T lymphocyte costimulation with cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4Ig) reverses the cellular pathology of psoriatic plaques, including the activation of keratinocytes, dendritic cells, and endothelial cells. J. Exp. Med. 192, 681–694 (2000).

    Article  CAS  Google Scholar 

  31. Wolk, K. et al. IL-22 increases the innate immunity of tissues. Immunity 21, 241–254 (2004).

    Article  CAS  Google Scholar 

  32. Finch, P. W., Murphy, F., Cardinale, I. & Krueger, J. G. Altered expression of keratinocyte growth factor and its receptor in psoriasis. Am. J. Pathol. 151, 1619–1628 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Bowcock, A. M. The genetics of psoriasis and autoimmunity. Annu. Rev. Genomics Hum. Genet. 6, 93–122 (2005).

    Article  CAS  Google Scholar 

  34. Elder, J. T. et al. The genetics of psoriasis. Arch. Dermatol. 130, 216–224 (1994).

    Article  CAS  Google Scholar 

  35. Tiilikainen, A., Lassus, A., Karvonen, J., Vartiainen, P. & Julin, M. Psoriasis and HLA-Cw6. Br. J. Dermatol. 102, 179–184 (1980).

    Article  CAS  Google Scholar 

  36. Veal, C. D. et al. Family-based analysis using a dense single-nucleotide polymorphism-based map defines genetic variation at PSORS1, the major psoriasis-susceptibility locus. Am. J. Hum. Genet. 71, 554–564 (2002).

    Article  CAS  Google Scholar 

  37. Nair, R. P. et al. Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene. Am. J. Hum. Genet. 78, 827–851 (2006).

    Article  CAS  Google Scholar 

  38. Helms, C. et al. Localization of PSORS1 to a haplotype block harboring HLA-C and distinct from corneodesmosin and HCR. Hum. Genet. 118, 466–476 (2005).

    Article  CAS  Google Scholar 

  39. Helms, C. et al. A putative RUNX1 binding site variant between SLC9A3R1 and NAT9 is associated with susceptibility to psoriasis. Nature Genet. 35, 349–356 (2003).

    Article  CAS  Google Scholar 

  40. Huffmeier, U. et al. Evidence for susceptibility determinant(s) to psoriasis vulgaris in or near PTPN22 in German patients. J. Med. Genet. 43, 517–522 (2006).

    Article  CAS  Google Scholar 

  41. Tsunemi, Y. et al. Interleukin-12 p40 gene (IL12B) 3′-untranslated region polymorphism is associated with susceptibility to atopic dermatitis and psoriasis vulgaris. J. Dermatol. Sci. 30, 161–166 (2002).

    Article  CAS  Google Scholar 

  42. Koks, S. et al. Combined haplotype analysis of the interleukin-19 and -20 genes: relationship to plaque-type psoriasis. Genes Immun. 5, 662–667 (2004).

    Article  CAS  Google Scholar 

  43. Foerster, J. et al. Evaluation of the IRF-2 gene as a candidate for PSORS3. J. Invest. Dermatol. 122, 61–64 (2004).

    Article  CAS  Google Scholar 

  44. Tomfohrde, J. et al. Gene for familial psoriasis susceptibility mapped to the distal end of human chromosome 17q. Science 264, 1141–1145 (1994).

    Article  ADS  CAS  Google Scholar 

  45. Hwu, W. L. et al. Mapping of psoriasis to 17q terminus. J. Med. Genet. 42, 152–158 (2005).

    Article  CAS  Google Scholar 

  46. Birnbaum, R. Y. et al. Seborrhea-like dermatitis with psoriasiform elements caused by a mutation in ZNF750, encoding a putative C2H2 zinc finger protein. Nature Genet. 38, 749–751 (2006).

    Article  CAS  Google Scholar 

  47. Nestle, F. O. & Nickoloff, B. J. From classical mouse models of psoriasis to a spontaneous xenograft model featuring use of AGR mice. Ernst Schering Res. Found. Workshop 203–212 (2005).

  48. Villadsen, L. S. et al. Resolution of psoriasis upon blockade of IL-15 biological activity in a xenograft mouse model. J. Clin. Invest. 112, 1571–1580 (2003).

    Article  CAS  Google Scholar 

  49. Weinberg, J. M., Bottino, C. J., Lindholm, J. & Buchholz, R. Biologic therapy for psoriasis: an update on the tumor necrosis factor inhibitors infliximab, etanercept, and adalimumab, and the T-cell-targeted therapies efalizumab and alefacept. J. Drugs Dermatol. 4, 544–555 (2005).

    PubMed  Google Scholar 

  50. Gottlieb, A. B. Psoriasis: emerging therapeutic strategies. Nature Rev. Drug Discov. 4, 19–34 (2005).

    Article  CAS  Google Scholar 

  51. Papp, K. A. The long-term efficacy and safety of new biological therapies for psoriasis. Arch. Dermatol. Res. 298, 7–15 (2006).

    Article  CAS  Google Scholar 

  52. Ellis, C. N. & Krueger, G. G. Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes. N. Engl. J. Med. 345, 248–255 (2001).

    Article  CAS  Google Scholar 

  53. Chamian, F. et al. Alefacept reduces infiltrating T cells, activated dendritic cells, and inflammatory genes in psoriasis vulgaris. Proc. Natl Acad. Sci. USA 102, 2075–2080 (2005).

    Article  ADS  CAS  Google Scholar 

  54. Vugmeyster, Y. et al. Efalizumab (anti-CD11a)-induced increase in leukocyte numbers in psoriasis patients is preferentially mediated by blocked entry of memory CD8+ T cells into the skin. Clin. Immunol. 113, 38–46 (2004).

    Article  CAS  Google Scholar 

  55. Gottlieb, A. B. et al. TNF inhibition rapidly down-regulates multiple proinflammatory pathways in psoriasis plaques. J. Immunol. 175, 2721–2729 (2005).

    Article  CAS  Google Scholar 

  56. Kruger-Krasagakis, S., Galanopoulos, V. K., Giannikaki, L., Stefanidou, M. & Tosca, A. D. Programmed cell death of keratinocytes in infliximab-treated plaque-type psoriasis. Br. J. Dermatol. 154, 460–466 (2006).

    Article  CAS  Google Scholar 

  57. Boruchov, A. M. et al. Activating and inhibitory IgG Fc receptors on human DCs mediate opposing functions. J. Clin. Invest. 115, 2914–2923 (2005).

    Article  CAS  Google Scholar 

  58. Dupasquier, M., Stoitzner, P., van Oudenaren, A., Romani, N. & Leenen, P. J. Macrophages and dendritic cells constitute a major subpopulation of cells in the mouse dermis. J. Invest. Dermatol. 123, 876–879 (2004).

    Article  CAS  Google Scholar 

  59. Chen, D. M., Gordon, K., Leonardi, C. & Menter, M. A. Adalimumab efficacy and safety in patients with moderate to severe chronic plaque psoriasis: preliminary findings from a 12-week dose-ranging trial. J. Am. Acad. Dermatol. 50, 1 (2004).

    Article  Google Scholar 

  60. Gottlieb, A. B. et al. Oral pimecrolimus in the treatment of moderate to severe chronic plaque-type psoriasis: a double-blind, multicentre, randomized, dose-finding trial. Br. J. Dermatol. 152, 1219–1227 (2005).

    Article  CAS  Google Scholar 

  61. Toichi, E. et al. An anti-IL-12p40 antibody down-regulates type 1 cytokines, chemokines, and IL-12/IL-23 in psoriasis. J. Immunol. 177, 4917–4926 (2006).

    Article  CAS  Google Scholar 

  62. Xia, Y. P. et al. Transgenic delivery of VEGF to mouse skin leads to an inflammatory condition resembling human psoriasis. Blood 102, 161–168 (2003).

    Article  CAS  Google Scholar 

  63. Blumberg, H. et al. Interleukin 20: discovery, receptor identification, and role in epidermal function. Cell 104, 9–19 (2001).

    Article  CAS  Google Scholar 

  64. Zenz, R. et al. Psoriasis-like skin disease and arthritis caused by inducible epidermal deletion of Jun proteins. Nature 437, 369–375 (2005).

    Article  ADS  CAS  Google Scholar 

  65. Haider, A. S., Duculan, J., Whynot, J. A. & Krueger, J. G. Increased JunB mRNA and protein expression in psoriasis vulgaris lesions. J. Invest. Dermatol. 126, 912–914 (2006).

    Article  CAS  Google Scholar 

  66. Zheng, Y. et al. Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature advance online publication (24 December 2006) doi:10.1038/nature05505.

    Article  Google Scholar 

Download references

Acknowledgements

The authors and their primary research have been supported by grants from the NIH.

Author information

Author notes

  1. J.G.K. (jgk@rockefeller.edu). Reprints and permissions information is available at npg.nature.com/reprintsandpermissions.

Authors and Affiliations

  1. Laboratory for Investigative Dermatology, The Rockefeller University, 1230 York Avenue, Box 178, New York, New York 10021, USA.,

    Michelle A. Lowes & James G. Krueger

  2. Department of Genetics, Washington University, School of Medicine, 4566 Scott Avenue, Saint Louis, 63110, Missouri, USA

    Anne M. Bowcock

Authors
  1. Michelle A. Lowes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anne M. Bowcock
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James G. Krueger
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

James Krueger acknowledges research support from several companies (Genentech, Serono, Amgen, Biogen, Protein Design Lab and Bristol-Myers) that market biological drugs for psoriasis.

Additional information

Note added in proof: A recent study66 shows that IL-23 induces marked hyperplasia in epidermal keratinocytes in murine skin, and results suggest that this effect is mediated to a significant extent through IL-22 produced by TH17 T cells. However, keratinocyte hyperplasia is still present on an Il22-null background, which suggests that IL-23 or other factors independent of IL-22 also stimulate keratinocyte proliferation.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lowes, M., Bowcock, A. & Krueger, J. Pathogenesis and therapy of psoriasis. Nature 445, 866–873 (2007). https://doi.org/10.1038/nature05663

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature05663

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing