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Psoriasis

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Immunology of the Skin

Abstract

Psoriasis vulgaris is a chronic, debilitating skin disease that affects millions of people worldwide. Although many components, including keratinocytes, dendritic cells (DCs), T cells, neutrophils, and endothelial cells are involved in psoriasis lesional skins, it is an inflammatory skin disease mainly mediated by T cells and DCs. Psoriatic skin contains diversified T cell and dendritic cell populations, such as interleukin (IL)-17–producing T (T17) cells, T helper (Th)1 cells, Th22 cells, Langerhans cells, plasmacytoid DCs, and myeloid DCs. These cells interact with each other then complete psoriasis lesions. Inflammatory myeloid DCs release IL-23 and IL-12 to activate T17 cells, Th1 cells, and Th22 cells, and to produce the cytokines IL-17, interferon-γ, tumor necrosis factor (TNF), and IL-22. These cytokines mediate effects on keratinocytes to amplify psoriatic inflammation. Therapeutic studies with anticytokine antibodies have shown the importance of the key cytokines IL-23, TNF, and IL-17 in this process. Genetic studies also point to the importance of IL-23 in psoriasis pathogenesis. These findings indicate the central role of the IL-23/T17 axis in psoriasis. Our current model for disease pathogenesis emphasizes the central role of IL-23 in controlling activation of lymphocytes that produce IL-17 and a number of emerging therapies for psoriasis are targeted to the IL-23/T17 response axis.

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References

  1. Abrams JR, Lebwohl MG et al (1999) CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris. J Clin Invest 103(9):1243–1252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bauer B, Krumbock N et al (2000) T cell expressed PKCtheta demonstrates cell-type selective function. Eur J Immunol 30(12):3645–3654

    Article  CAS  PubMed  Google Scholar 

  3. Bos JD, de Rie MA et al (2005) Psoriasis: dysregulation of innate immunity. Br J Dermatol 152(6):1098–1107

    Article  CAS  PubMed  Google Scholar 

  4. Bowcock AM (2005) The genetics of psoriasis and autoimmunity. Annu Rev Genomics Hum Genet 6:93–122

    Article  CAS  PubMed  Google Scholar 

  5. Cameron AL, Kirby B et al (2002) Natural killer and natural killer-T cells in psoriasis. Arch Dermatol Res 294(8):363–369

    CAS  PubMed  Google Scholar 

  6. Chamian F, Lin SL et al (2007) Alefacept (anti-CD2) causes a selective reduction in circulating effector memory T cells (Tem) and relative preservation of central memory T cells (Tcm) in psoriasis. J Transl Med 5:27

    Article  PubMed  PubMed Central  Google Scholar 

  7. Chamian F, Lowes MA et al (2005) Alefacept reduces infiltrating T cells, activated dendritic cells, and inflammatory genes in psoriasis vulgaris. Proc Natl Acad Sci U S A 102(6):2075–2080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Chiricozzi A, Guttman-Yassky E et al (2011) Integrative responses to IL-17 and TNF-alpha in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis. J Invest Dermatol 131(3):677–687

    Article  CAS  PubMed  Google Scholar 

  9. Conti M, Beavo J (2007) Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling. Annu Rev Biochem 76:481–511

    Article  CAS  PubMed  Google Scholar 

  10. Di Meglio P, Di Cesare A et al (2011) The IL23R R381Q gene variant protects against immune-mediated diseases by impairing IL-23-induced Th17 effector response in humans. PLoS ONE 6(2):e17160

    Article  PubMed  PubMed Central  Google Scholar 

  11. Elder JT (2006) PSORS1: linking genetics and immunology. J Invest Dermatol 126(6):1205–1206

    Article  CAS  PubMed  Google Scholar 

  12. Ellis CN, Gorsulowsky DC et al (1986) Cyclosporine improves psoriasis in a double-blind study. JAMA 256(22):3110–3116

    Article  CAS  PubMed  Google Scholar 

  13. Eyerich S, Eyerich K et al (2009) Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling. J Clin Invest 119(12):3573–3585

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Finch PW, Murphy F et al (1997) Altered expression of keratinocyte growth factor and its receptor in psoriasis. Am J Pathol 151(6):1619–1628

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Fuentes-Duculan J, Suarez-Farinas M et al (2010) A subpopulation of CD163-positive macrophages is classically activated in psoriasis. J Invest Dermatol 130(10):2412–2422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gaffen SL (2009) Structure and signalling in the IL-17 receptor family. Nat Rev Immunol 9(8):556–567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ganguly D, Chamilos G et al (2009) Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J Exp Med 206(9):1983–1994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Genovese MC, Van den Bosch F et al (2010) LY2439821, a humanized anti-interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: a phase I randomized, double-blind, placebo-controlled, proof-of-concept study. Arthritis Rheum 62(4):929–939

    Article  CAS  PubMed  Google Scholar 

  19. Gilliet M, Lande R (2008) Antimicrobial peptides and self-DNA in autoimmune skin inflammation. Curr Opin Immunol 20(4):401–407

    Article  CAS  PubMed  Google Scholar 

  20. Gordon KB, Langley RG et al (2012) A phase III, randomized, controlled trial of the fully human IL-12/23 mAb briakinumab in moderate-to-severe psoriasis. J Invest Dermatol 132(2):304–314

    Article  CAS  PubMed  Google Scholar 

  21. Gottlieb AB, Leonardi C et al (2011) Efficacy and safety of briakinumab vs. etanercept and placebo in patients with moderate to severe chronic plaque psoriasis. Br J Dermatol 165(3):652–660

    Article  CAS  PubMed  Google Scholar 

  22. Gottlieb AB, Matheson RT et al (2013) Efficacy, tolerability, and pharmacodynamics of apremilast in recalcitrant plaque psoriasis: a phase II ppen-label study. J Drugs Dermatol 12(8):888–897

    CAS  PubMed  Google Scholar 

  23. Gottlieb SL, Gilleaudeau P et al (1995) Response of psoriasis to a lymphocyte-selective toxin (DAB389IL-2) suggests a primary immune, but not keratinocyte, pathogenic basis. Nat Med 1(5):442–447

    Article  CAS  PubMed  Google Scholar 

  24. Guo B, Su TT et al (2004) Protein kinase C family functions in B-cell activation. Curr Opin Immunol 16(3):367–373

    Article  CAS  PubMed  Google Scholar 

  25. Gupta AK, Fisher GJ et al (1989) Topical cyclosporine A inhibits the phorbol ester induced hyperplastic inflammatory response but not protein kinase C activation in mouse epidermis. J Invest Dermatol 93(3):379–386

    Article  CAS  PubMed  Google Scholar 

  26. Haider AS, Lowes MA et al (2008) Identification of cellular pathways of “type 1,” Th17 T cells, and TNF- and inducible nitric oxide synthase-producing dendritic cells in autoimmune inflammation through pharmacogenomic study of cyclosporine A in psoriasis. J Immunol 180(3):1913–1920

    Article  CAS  PubMed  Google Scholar 

  27. Houslay MD, Schafer P et al (2005) Keynote review: phosphodiesterase-4 as a therapeutic target. Drug Discov Today 10(22):1503–1519

    Article  CAS  PubMed  Google Scholar 

  28. Hueber W, Patel DD et al (2010) Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med 2(52):52ra72

    Article  PubMed  Google Scholar 

  29. Johnson-Huang LM, Suarez-Farinas M et al (2010) Effective narrow-band UVB radiation therapy suppresses the IL-23/IL-17 axis in normalized psoriasis plaques. J Invest Dermatol 130(11):2654–2663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Krueger JG, Fretzin S et al (2012) IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis. J Allergy Clin Immunol 130(1):145–154 e149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lande R, Gregorio J et al (2007) Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 449(7162):564–569

    Article  CAS  PubMed  Google Scholar 

  32. Lee E, Trepicchio WL et al (2004) Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. J Exp Med 199(1):125–130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Leonardi C, Matheson R et al (2012) Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med 366(13):1190–1199

    Article  CAS  PubMed  Google Scholar 

  34. Leonardi CL, Kimball AB et al (2008) Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet 371(9625):1665–1674

    Article  CAS  PubMed  Google Scholar 

  35. Lew W, Bowcock AM et al (2004) Psoriasis vulgaris: cutaneous lymphoid tissue supports T-cell activation and “Type 1” inflammatory gene expression. Trends Immunol 25(6):295–305

    Article  CAS  PubMed  Google Scholar 

  36. Liang SC, Tan XY et al (2006) Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 203(10):2271–2279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Liu Y, Helms C et al (2008) A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci. PLoS Genet 4(3):e1000041

    Article  PubMed  PubMed Central  Google Scholar 

  38. Lowes MA, Chamian F et al (2005) Increase in TNF-alpha and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a). Proc Natl Acad Sci U S A 102(52):19057–19062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Lowes MA, Kikuchi T et al (2008) Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol 128(5):1207–1211

    Article  CAS  PubMed  Google Scholar 

  40. Lowes MA, Russell CB et al (2013) The IL-23/T17 pathogenic axis in psoriasis is amplified by keratinocyte responses. Trends Immunol 34(4):174–181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Marrakchi S, Guigue P et al (2011) Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med 365(7):620–628

    Article  CAS  PubMed  Google Scholar 

  42. Mecklenbrauker I, Saijo K et al (2002) Protein kinase Cdelta controls self-antigen-induced B-cell tolerance. Nature 416(6883):860–865

    Article  PubMed  Google Scholar 

  43. Monks CR, Kupfer H et al (1997) Selective modulation of protein kinase C-theta during T-cell activation. Nature 385(6611):83–86

    Article  CAS  PubMed  Google Scholar 

  44. Nair RP, Duffin KC et al (2009) Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet 41(2):199–204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Nair RP, Ruether A et al (2008) Polymorphisms of the IL12B and IL23R genes are associated with psoriasis. J Invest Dermatol 128(7):1653–1661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Nestle FO, Conrad C et al (2005) Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production. J Exp Med 202(1):135–143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Nograles KE, Krueger JG (2011) Anti-cytokine therapies for psoriasis. Exp Cell Res 317(9):1293–1300

    Article  CAS  PubMed  Google Scholar 

  48. Nograles KE, Zaba LC et al (2008) Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways. Br J Dermatol 159(5):1092–1102

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Onoufriadis A, Simpson MA et al (2011) Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis. Am J Hum Genet 89(3):432–437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Page CP, Spina D (2011) Phosphodiesterase inhibitors in the treatment of inflammatory diseases. Handb Exp Pharmacol 204:391–414

    Google Scholar 

  51. Papp KA, Langley RG et al (2008) Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet 371(9625):1675–1684

    Article  CAS  PubMed  Google Scholar 

  52. Papp KA, Leonardi C et al (2012) Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis. N Engl J Med 366(13):1181–1189

    Article  CAS  PubMed  Google Scholar 

  53. Papp KA, Reid C et al (2012) Anti-IL-17 receptor antibody AMG 827 leads to rapid clinical response in subjects with moderate to severe psoriasis: results from a phase I, randomized, placebo-controlled trial. J Invest Dermatol 132(10):2466–2469

    Article  CAS  PubMed  Google Scholar 

  54. Peric M, Koglin S et al (2008) IL-17A enhances vitamin D3-induced expression of cathelicidin antimicrobial peptide in human keratinocytes. J Immunol 181(12):8504–8512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Sa SM, Valdez PA et al (2007) The effects of IL-20 subfamily cytokines on reconstituted human epidermis suggest potential roles in cutaneous innate defense and pathogenic adaptive immunity in psoriasis. J Immunol 178(4):2229–2240

    Article  CAS  PubMed  Google Scholar 

  56. Schafer PH, Parton A et al (2010) Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis. Br J Pharmacol 159(4):842–855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Shen F, Hu Z et al (2006) Identification of common transcriptional regulatory elements in interleukin-17 target genes. J Biol Chem 281(34):24138–24148

    Article  CAS  PubMed  Google Scholar 

  58. Skvara H, Dawid M et al (2008) The PKC inhibitor AEB071 may be a therapeutic option for psoriasis. J Clin Invest 118(9):3151–3159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Spitaler M, Cantrell DA (2004) Protein kinase C and beyond. Nat Immunol 5(8):785–790

    Article  CAS  PubMed  Google Scholar 

  60. Strober BE, Crowley JJ et al (2011) Efficacy and safety results from a phase III, randomized controlled trial comparing the safety and efficacy of briakinumab with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis. Br J Dermatol 165(3):661–668

    Article  CAS  PubMed  Google Scholar 

  61. Suarez-Farinas M, Li K et al (2012) Expanding the psoriasis disease profile: interrogation of the skin and serum of patients with moderate-to-severe psoriasis. J Invest Dermatol 132(11):2552–2564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Swindell WR, Xing X et al (2012) Heterogeneity of inflammatory and cytokine networks in chronic plaque psoriasis. PLoS ONE 7(3):e34594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Tian S, Krueger JG et al (2012) Meta-analysis derived (MAD) transcriptome of psoriasis defines the “core” pathogenesis of disease. PLoS ONE 7(9):e44274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. van der Fits L, Mourits S et al (2009) Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J Immunol 182(9):5836–5845

    Article  PubMed  Google Scholar 

  65. Wang F, Lee E et al (2006) Prominent production of IL-20 by CD68+/CD11c+ myeloid-derived cells in psoriasis: gene regulation and cellular effects. J Invest Dermatol 126(7):1590–1599

    Article  CAS  PubMed  Google Scholar 

  66. Wolk K, Witte E et al (2009) The Th17 cytokine IL-22 induces IL-20 production in keratinocytes: a novel immunological cascade with potential relevance in psoriasis. Eur J Immunol 39(12):3570–3581

    Article  CAS  PubMed  Google Scholar 

  67. Zaba LC, Cardinale I et al (2007) Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses. J Exp Med 204(13):3183–3194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Zaba LC, Fuentes-Duculan J et al (2009) Psoriasis is characterized by accumulation of immunostimulatory and Th1/Th17 cell-polarizing myeloid dendritic cells. J Invest Dermatol 129(1):79–88

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Zaba LC, Fuentes-Duculan J et al (2010) Identification of TNF-related apoptosis-inducing ligand and other molecules that distinguish inflammatory from resident dendritic cells in patients with psoriasis. J Allergy Clin Immunol 125(6):1261–1268 e1269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Zaba LC, Fuentes-Duculan J et al (2007) Normal human dermis contains distinct populations of CD11c+BDCA-1+ dendritic cells and CD163+FXIIIA+ macrophages. J Clin Invest 117(9):2517–2525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Zaba LC, Krueger JG et al (2009) Resident and “inflammatory” dendritic cells in human skin. J Invest Dermatol 129(2):302–308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Zaba LC, Suarez-Farinas M et al (2009) Effective treatment of psoriasis with etanercept is linked to suppression of IL-17 signaling, not immediate response TNF genes. J Allergy Clin Immunol 124(5):1022–1030.e395

    Google Scholar 

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Authors and Affiliations

  1. Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA

    Hanako Ohmatsu & James G. Krueger

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  1. Hanako Ohmatsu
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  2. James G. Krueger
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Correspondence to James G. Krueger .

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  1. Department of Dermatology, Kyoto University Grad Sch of Med., Sakyo-ku, Kyoto, Japan

    Kenji Kabashima

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Ohmatsu, H., Krueger, J.G. (2016). Psoriasis. In: Kabashima, K. (eds) Immunology of the Skin. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55855-2_22

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