IL-23/TH17 Pathway in Psoriasis and Inflammatory Skin Diseases

  • Kristine E. Nograles
  • Batya Davidovici
  • James G. Krueger


Psoriasis is a highly prevalent and heritable skin disease that affects the population worldwide. While the importance of activated T cells in disease pathogenesis has long been appreciated, the central role of the IL-23/TH17 pathway has only recently been realized. In this chapter, we discuss the contributions of TH17 cells in psoriasis, as well as in other inflammatory skin diseases.


Atopic Dermatitis Psoriatic Lesion TH17 Pathway Chronic Mucocutaneous Candidiasis Psoriasis Lesion 
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.



This publication was made possible by grant number 5UL1RR024143 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. JGK has received research grants from Amgen, Centocor, Wyeth and Eli Lilly for the study of therapeutic agents related to the IL-23/TH17 pathway.


  1. Abrams, J. R., S. L. Kelley, E. Hayes, T. Kikuchi, M. J. Brown, S. Kang, M. G. Lebwohl, C. A. Guzzo, B. V. Jegasothy, P. S. Linsley, and J. G. Krueger. 2000. 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 (5):681–94.PubMedCrossRefGoogle Scholar
  2. Albanesi, C., A. Cavani, and G. Girolomoni. 1999. IL-17 is produced by nickel-specific T lymphocytes and regulates ICAM-1 expression and chemokine production in human keratinocytes: synergistic or antagonist effects with IFN-gamma and TNF-alpha. J Immunol 162 (1):494–502.PubMedGoogle Scholar
  3. Arican, O., M. Aral, S. Sasmaz, and P. Ciragil. 2005. Serum levels of TNF-alpha, IFN-gamma, IL-6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis and correlation with disease severity. Mediators Inflamm 2005 (5):273–9.PubMedCrossRefGoogle Scholar
  4. Austin, L. M., M. Ozawa, T. Kikuchi, I. B. Walters, and J. G. Krueger. 1999. The majority of epidermal T cells in Psoriasis vulgaris lesions can produce type 1 cytokines, interferon-gamma, interleukin-2, and tumor necrosis factor-alpha, defining TC1 (cytotoxic T lymphocyte) and TH1 effector populations: a type 1 differentiation bias is also measured in circulating blood T cells in psoriatic patients. J Invest Dermatol 113 (5):752–9.PubMedCrossRefGoogle Scholar
  5. Bettelli, E., T. Korn, and V. K. Kuchroo. 2007. Th17: the third member of the effector T cell trilogy. Curr Opin Immunol 19 (6):652–7.PubMedCrossRefGoogle Scholar
  6. Boniface, K., E. Guignouard, N. Pedretti, M. Garcia, A. Delwail, F. X. Bernard, F. Nau, G. Guillet, G. Dagregorio, H. Yssel, J. C. Lecron, and F. Morel. 2007. A role for T cell-derived interleukin 22 in psoriatic skin inflammation. Clin Exp Immunol 150 (3):407–15.PubMedCrossRefGoogle Scholar
  7. Brandrup, F., N. Holm, N. Grunnet, K. Henningsen, and H. E. Hansen. 1982. Psoriasis in monozygotic twins: variations in expression in individuals with identical genetic constitution. Acta Derm Venereol 62 (3):229–36.PubMedGoogle Scholar
  8. Cargill, M., S. J. Schrodi, M. Chang, V. E. Garcia, R. Brandon, K. P. Callis, N. Matsunami, K. G. Ardlie, D. Civello, J. J. Catanese, D. U. Leong, J. M. Panko, L. B. McAllister, C. B. Hansen, J. Papenfuss, S. M. Prescott, T. J. White, M. F. Leppert, G. G. Krueger, and A. B. Begovich. 2007. A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet 80 (2):273–90.PubMedCrossRefGoogle Scholar
  9. Caruso, R., E. Botti, M. Sarra, M. Esposito, C. Stolfi, L. Diluvio, M. L. Giustizieri, V. Pacciani, A. Mazzotta, E. Campione, T. T. Macdonald, S. Chimenti, F. Pallone, A. Costanzo, and G. Monteleone. 2009. Involvement of interleukin-21 in the epidermal hyperplasia of psoriasis. Nat Med 15 (9):1013–5.PubMedCrossRefGoogle Scholar
  10. Chang, S. H., and C. Dong. 2007. A novel heterodimeric cytokine consisting of IL-17 and IL-17F regulates inflammatory responses. Cell Res 17 (5):435–40.PubMedGoogle Scholar
  11. Christophers, E. 2001. Psoriasis--epidemiology and clinical spectrum. Clin Exp Dermatol 26 (4):314–20.PubMedCrossRefGoogle Scholar
  12. Ciric, B., M. El-behi, R. Cabrera, G. X. Zhang, and A. Rostami. 2009. IL-23 drives pathogenic IL-17-producing CD8+ T cells. J Immunol 182 (9):5296–305.PubMedCrossRefGoogle Scholar
  13. Corrigall, V. M., M. Arastu, S. Khan, C. Shah, M. Fife, T. Smeets, P. P. Tak, and G. S. Panayi. 2001. Functional IL-2 receptor beta (CD122) and gamma (CD132) chains are expressed by fibroblast-like synoviocytes: activation by IL-2 stimulates monocyte chemoattractant protein-1 production. J Immunol 166 (6):4141–7.PubMedGoogle Scholar
  14. Csiszar, A., Z. Ungvari, A. Koller, J. G. Edwards, and G. Kaley. 2003. Aging-induced proinflammatory shift in cytokine expression profile in coronary arteries. FASEB J 17 (9):1183–5.PubMedGoogle Scholar
  15. de Jongh, G. J., P. L. Zeeuwen, M. Kucharekova, R. Pfundt, P. G. van der Valk, W. Blokx, A. Dogan, P. S. Hiemstra, P. C. van de Kerkhof, and J. Schalkwijk. 2005. High expression levels of keratinocyte antimicrobial proteins in psoriasis compared with atopic dermatitis. J Invest Dermatol 125 (6):1163–73.CrossRefGoogle Scholar
  16. Di Cesare, A., P. Di Meglio, and F. O. Nestle. 2009. The IL-23/Th17 axis in the immunopathogenesis of psoriasis. J Invest Dermatol 129 (6):1339–50.PubMedCrossRefGoogle Scholar
  17. Duerr, R. H., K. D. Taylor, S. R. Brant, J. D. Rioux, M. S. Silverberg, M. J. Daly, A. H. Steinhart, C. Abraham, M. Regueiro, A. Griffiths, T. Dassopoulos, A. Bitton, H. Yang, S. Targan, L. W. Datta, E. O. Kistner, L. P. Schumm, A. T. Lee, P. K. Gregersen, M. M. Barmada, J. I. Rotter, D. L. Nicolae, and J. H. Cho. 2006. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314 (5804):1461–3.PubMedCrossRefGoogle Scholar
  18. Duhen, T., R. Geiger, D. Jarrossay, A. Lanzavecchia, and F. Sallusto. 2009. Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells. Nat Immunol 10 (8):857–63.PubMedCrossRefGoogle Scholar
  19. Elder, J. T., A. T. Bruce, J. E. Gudjonsson, A. Johnston, P. E. Stuart, T. Tejasvi, J. J. Voorhees, G. R. Abecasis, and R. P. Nair. 2010. Molecular Dissection of Psoriasis: Integrating Genetics and Biology. J Invest Dermatol 130 (5):1213–26.Google Scholar
  20. Ellis, C. N., D. C. Gorsulowsky, T. A. Hamilton, J. K. Billings, M. D. Brown, J. T. Headington, K. D. Cooper, O. Baadsgaard, E. A. Duell, T. M. Annesley, and et al. 1986. Cyclosporine improves psoriasis in a double-blind study. JAMA 256 (22):3110–6.PubMedCrossRefGoogle Scholar
  21. Farber, E. M., M. L. Nall, and W. Watson. 1974. Natural history of psoriasis in 61 twin pairs. Arch Dermatol 109 (2):207–11.PubMedCrossRefGoogle Scholar
  22. Farber, E.M., and M.L. Nall. 1998. Epidemiology: natural history and genetics. In Psoriasis, edited by H. H. Roenigk and H. I. Maibach. New York: Marcel Dekker.Google Scholar
  23. Ferenczi, K., L. Burack, M. Pope, J. G. Krueger, and L. M. Austin. 2000. CD69, HLA-DR and the IL-2R identify persistently activated T cells in psoriasis vulgaris lesional skin: blood and skin comparisons by flow cytometry. J Autoimmun 14 (1):63–78.PubMedCrossRefGoogle Scholar
  24. Fossiez, F., O. Djossou, P. Chomarat, L. Flores-Romo, S. Ait-Yahia, C. Maat, J. J. Pin, P. Garrone, E. Garcia, S. Saeland, D. Blanchard, C. Gaillard, B. Das Mahapatra, E. Rouvier, P. Golstein, J. Banchereau, and S. Lebecque. 1996. T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J Exp Med 183 (6):2593–603.PubMedCrossRefGoogle Scholar
  25. Fuhlbrigge, R. C., J. D. Kieffer, D. Armerding, and T. S. Kupper. 1997. Cutaneous lymphocyte antigen is a specialized form of PSGL-1 expressed on skin-homing T cells. Nature 389 (6654):978–81.PubMedCrossRefGoogle Scholar
  26. Fujita, H., K.E. Nograles, T. Kikuchi, J. Gonzalez, J.A. Carucci, and J.G. Krueger. 2009. Human Langerhans cells induce distinct IL-22-producing CD4+ T cells lacking IL-17 production. Proc Natl Acad Sci USA 106 (51):21795–800.PubMedCrossRefGoogle Scholar
  27. Gaffen, S. L. 2009. Structure and signalling in the IL-17 receptor family. Nat Rev Immunol 9 (8):556–67.PubMedCrossRefGoogle Scholar
  28. Ganguly, D., G. Chamilos, R. Lande, J. Gregorio, S. Meller, V. Facchinetti, B. Homey, F. J. Barrat, T. Zal, and M. Gilliet. 2009. Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J Exp Med 206 (9):1983–94.PubMedCrossRefGoogle Scholar
  29. Gelfand, J. M., A. B. Troxel, J. D. Lewis, S. K. Kurd, D. B. Shin, X. Wang, D. J. Margolis, and B. L. Strom. 2007. The risk of mortality in patients with psoriasis: results from a population-based study. Arch Dermatol 143 (12):1493–9.PubMedCrossRefGoogle Scholar
  30. Gelfand, J. M., R. Weinstein, S. B. Porter, A. L. Neimann, J. A. Berlin, and D. J. Margolis. 2005. Prevalence and treatment of psoriasis in the United Kingdom: a population-based study. Arch Dermatol 141 (12):1537–41.PubMedCrossRefGoogle Scholar
  31. Gottlieb, A. B., F. Chamian, S. Masud, I. Cardinale, M. V. Abello, M. A. Lowes, F. Chen, M. Magliocco, and J. G. Krueger. 2005. TNF inhibition rapidly down-regulates multiple proinflammatory pathways in psoriasis plaques. J Immunol 175 (4):2721–9.PubMedGoogle Scholar
  32. Gottlieb, S. L., P. Gilleaudeau, R. Johnson, L. Estes, T. G. Woodworth, A. B. Gottlieb, and J. G. Krueger. 1995. Response of psoriasis to a lymphocyte-selective toxin (DAB389IL-2) suggests a primary immune, but not keratinocyte, pathogenic basis. Nat Med 1 (5):442–7.PubMedCrossRefGoogle Scholar
  33. Griffiths, C. E., E. Christophers, J. N. Barker, R. J. Chalmers, S. Chimenti, G. G. Krueger, C. Leonardi, A. Menter, J. P. Ortonne, and L. Fry. 2007. A classification of psoriasis vulgaris according to phenotype. Br J Dermatol 156 (2):258–62.PubMedCrossRefGoogle Scholar
  34. Griffiths, C.E.M., R.D.R. Camp, and J.N.W.N. Barker. 2004. Psoriasis. In Rook’s Textbook of Dermatology, edited by T. Burns, S. Breathnach, N. Cox and C. Griffiths. Oxford: Blackwell Publishing.Google Scholar
  35. Guttman-Yassky, E., M. A. Lowes, J. Fuentes-Duculan, L. C. Zaba, I. Cardinale, K. E. Nograles, A. Khatcherian, I. Novitskaya, J. A. Carucci, R. Bergman, and J. G. Krueger. 2008. Low expression of the IL-23/Th17 pathway in atopic dermatitis compared to psoriasis. J Immunol 181 (10):7420–7.PubMedGoogle Scholar
  36. Habib, T., S. Senadheera, K. Weinberg, and K. Kaushansky. 2002. The common gamma chain (gamma c) is a required signaling component of the IL-21 receptor and supports IL-21-induced cell proliferation via JAK3. Biochemistry 41 (27):8725–31.PubMedCrossRefGoogle Scholar
  37. Haider, A. S., M. A. Lowes, M. Suarez-Farinas, L. C. Zaba, I. Cardinale, A. Khatcherian, I. Novitskaya, K. M. Wittkowski, and J. G. Krueger. 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):1913–20.PubMedGoogle Scholar
  38. Harper, E. G., C. Guo, H. Rizzo, J. V. Lillis, S. E. Kurtz, I. Skorcheva, D. Purdy, E. Fitch, M. Iordanov, and A. Blauvelt. 2009. Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo: implications for psoriasis pathogenesis. J Invest Dermatol 129 (9):2175–83.PubMedCrossRefGoogle Scholar
  39. Hashmi, S., and Q. T. Zeng. 2006. Role of interleukin-17 and interleukin-17-induced cytokines interleukin-6 and interleukin-8 in unstable coronary artery disease. Coron Artery Dis 17 (8):699–706.PubMedCrossRefGoogle Scholar
  40. Hedrick, M. N., A. S. Lonsdorf, A. K. Shirakawa, C. C. Richard Lee, F. Liao, S. P. Singh, H. H. Zhang, A. Grinberg, P. E. Love, S. T. Hwang, and J. M. Farber. 2009. CCR6 is required for IL-23-induced psoriasis-like inflammation in mice. J Clin Invest 119 (8):2317–29.PubMedCrossRefGoogle Scholar
  41. Henseler, T., and E. Christophers. 1985. Psoriasis of early and late onset: characterization of two types of psoriasis vulgaris. J Am Acad Dermatol 13 (3):450–6.PubMedCrossRefGoogle Scholar
  42. Hollox, E. J., U. Huffmeier, P. L. Zeeuwen, R. Palla, J. Lascorz, D. Rodijk-Olthuis, P. C. van de Kerkhof, H. Traupe, G. de Jongh, M. den Heijer, A. Reis, J. A. Armour, and J. Schalkwijk. 2008. Psoriasis is associated with increased beta-defensin genomic copy number. Nat Genet 40 (1):23–5.PubMedCrossRefGoogle Scholar
  43. Homey, B., M. C. Dieu-Nosjean, A. Wiesenborn, C. Massacrier, J. J. Pin, E. Oldham, D. Catron, M. E. Buchanan, A. Muller, R. deWaal Malefyt, G. Deng, R. Orozco, T. Ruzicka, P. Lehmann, S. Lebecque, C. Caux, and A. Zlotnik. 2000. Up-regulation of macrophage inflammatory protein-3 alpha/CCL20 and CC chemokine receptor 6 in psoriasis. J Immunol 164 (12):6621–32.PubMedGoogle Scholar
  44. Ishigame, H., S. Kakuta, T. Nagai, M. Kadoki, A. Nambu, Y. Komiyama, N. Fujikado, Y. Tanahashi, A. Akitsu, H. Kotaki, K. Sudo, S. Nakae, C. Sasakawa, and Y. Iwakura. 2009. Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity 30 (1):108–19.PubMedCrossRefGoogle Scholar
  45. Kenney, J.A. 1971. Psoriasis in the American black. In Psoriasis: Proceedings of the International Symposium. Stanford, California: Stanford University Press.Google Scholar
  46. Koga, C., K. Kabashima, N. Shiraishi, M. Kobayashi, and Y. Tokura. 2008. Possible pathogenic role of Th17 cells for atopic dermatitis. J Invest Dermatol 128 (11):2625–30.PubMedCrossRefGoogle Scholar
  47. Kryczek, I., A. T. Bruce, J. E. Gudjonsson, A. Johnston, A. Aphale, L. Vatan, W. Szeliga, Y. Wang, Y. Liu, T. H. Welling, J. T. Elder, and W. Zou. 2008. Induction of IL-17+ T cell trafficking and development by IFN-gamma: mechanism and pathological relevance in psoriasis. J Immunol 181 (7):4733–41.PubMedGoogle Scholar
  48. Kuestner, R. E., D. W. Taft, A. Haran, C. S. Brandt, T. Brender, K. Lum, B. Harder, S. Okada, C. D. Ostrander, J. L. Kreindler, S. J. Aujla, B. Reardon, M. Moore, P. Shea, R. Schreckhise, T. R. Bukowski, S. Presnell, P. Guerra-Lewis, J. Parrish-Novak, J. L. Ellsworth, S. Jaspers, K. E. Lewis, M. Appleby, J. K. Kolls, M. Rixon, J. W. West, Z. Gao, and S. D. Levin. 2007. Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F. J Immunol 179 (8):5462–73.PubMedGoogle Scholar
  49. Lande, R., J. Gregorio, V. Facchinetti, B. Chatterjee, Y. H. Wang, B. Homey, W. Cao, B. Su, F. O. Nestle, T. Zal, I. Mellman, J. M. Schroder, Y. J. Liu, and M. Gilliet. 2007. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 449 (7162):564–9.PubMedCrossRefGoogle Scholar
  50. Larsen, J. M., C. M. Bonefeld, S. S. Poulsen, C. Geisler, and L. Skov. 2009. IL-23 and T(H)17-mediated inflammation in human allergic contact dermatitis. J Allergy Clin Immunol 123 (2):486–92.PubMedCrossRefGoogle Scholar
  51. Lee, E., W. L. Trepicchio, J. L. Oestreicher, D. Pittman, F. Wang, F. Chamian, M. Dhodapkar, and J. G. Krueger. 2004. Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. J Exp Med 199 (1):125–30.PubMedCrossRefGoogle Scholar
  52. Leonardi, C. L., A. B. Kimball, K. A. Papp, N. Yeilding, C. Guzzo, Y. Wang, S. Li, L. T. Dooley, and K. B. Gordon. 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):1665–74.PubMedCrossRefGoogle Scholar
  53. Leung, D. Y., and T. Bieber. 2003. Atopic dermatitis. Lancet 361 (9352):151–60.PubMedCrossRefGoogle Scholar
  54. Lew, W., A. M. Bowcock, and J. G. Krueger. 2004. Psoriasis vulgaris: cutaneous lymphoid tissue supports T-cell activation and “Type 1” inflammatory gene expression. Trends Immunol 25 (6):295–305.PubMedCrossRefGoogle Scholar
  55. Lew, W., E. Lee, and J. G. Krueger. 2004. Psoriasis genomics: analysis of proinflammatory (type 1) gene expression in large plaque (Western) and small plaque (Asian) psoriasis vulgaris.Br J Dermatol 150 (4):668–76.PubMedCrossRefGoogle Scholar
  56. Li, J., D. Li, and Z. Tan. 2004. The expression of interleukin-17, interferon-gamma, and macrophage inflammatory protein-3 alpha mRNA in patients with psoriasis vulgaris. J Huazhong Univ Sci Technolog Med Sci 24 (3):294–6.PubMedCrossRefGoogle Scholar
  57. Liang, S. C., X. Y. Tan, D. P. Luxenberg, R. Karim, K. Dunussi-Joannopoulos, M. Collins, and L. A. Fouser. 2006. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 203 (10):2271–9.PubMedCrossRefGoogle Scholar
  58. Liu, Y., C. Helms, W. Liao, L. C. Zaba, S. Duan, J. Gardner, C. Wise, A. Miner, M. J. Malloy, C. R. Pullinger, J. P. Kane, S. Saccone, J. Worthington, I. Bruce, P. Y. Kwok, A. Menter, J. Krueger, A. Barton, N. L. Saccone, and A. M. Bowcock. 2008. A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci. PLoS Genet 4 (3):e1000041.PubMedCrossRefGoogle Scholar
  59. Lopez-Candales, A. 2001. Metabolic syndrome X: a comprehensive review of the pathophysiology and recommended therapy. J Med 32 (5–6):283–300.PubMedGoogle Scholar
  60. Lowes, M. A., F. Chamian, M. V. Abello, J. Fuentes-Duculan, S. L. Lin, R. Nussbaum, I. Novitskaya, H. Carbonaro, I. Cardinale, T. Kikuchi, P. Gilleaudeau, M. Sullivan-Whalen, K. M. Wittkowski, K. Papp, M. Garovoy, W. Dummer, R. M. Steinman, and J. G. Krueger. 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):19057–62.PubMedCrossRefGoogle Scholar
  61. Lowes, M. A., T. Kikuchi, J. Fuentes-Duculan, I. Cardinale, L. C. Zaba, A. S. Haider, E. P. Bowman, and J. G. Krueger. 2008. Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol 128 (5):1207–11.PubMedCrossRefGoogle Scholar
  62. Manel, N., D. Unutmaz, and D. R. Littman. 2008. The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat. Nat Immunol 9 (6):641–9.PubMedCrossRefGoogle Scholar
  63. Milner, J. D., J. M. Brenchley, A. Laurence, A. F. Freeman, B. J. Hill, K. M. Elias, Y. Kanno, C. Spalding, H. Z. Elloumi, M. L. Paulson, J. Davis, A. Hsu, A. I. Asher, J. O’Shea, S. M. Holland, W. E. Paul, and D. C. Douek. 2008. Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 452 (7188):773–6.PubMedCrossRefGoogle Scholar
  64. Morganroth, G. S., L. S. Chan, G. D. Weinstein, J. J. Voorhees, and K. D. Cooper. 1991. Proliferating cells in psoriatic dermis are comprised primarily of T cells, endothelial cells, and factor XIIIa+ perivascular dendritic cells. J Invest Dermatol 96 (3):333–40.PubMedCrossRefGoogle Scholar
  65. Nair, R. P., K. C. Duffin, C. Helms, J. Ding, P. E. Stuart, D. Goldgar, J. E. Gudjonsson, Y. Li, T. Tejasvi, B. J. Feng, A. Ruether, S. Schreiber, M. Weichenthal, D. Gladman, P. Rahman, S. J. Schrodi, S. Prahalad, S. L. Guthery, J. Fischer, W. Liao, P. Y. Kwok, A. Menter, G. M. Lathrop, C. A. Wise, A. B. Begovich, J. J. Voorhees, J. T. Elder, G. G. Krueger, A. M. Bowcock, and G. R. Abecasis. 2009. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet 41 (2):199–204.PubMedCrossRefGoogle Scholar
  66. Nair, R. P., A. Ruether, P. E. Stuart, S. Jenisch, T. Tejasvi, R. Hiremagalore, S. Schreiber, D. Kabelitz, H. W. Lim, J. J. Voorhees, E. Christophers, J. T. Elder, and M. Weichenthal. 2008. Polymorphisms of the IL12B and IL23R genes are associated with psoriasis. J Invest Dermatol 128 (7):1653–61.PubMedCrossRefGoogle Scholar
  67. Nestle, F. O., C. Conrad, A. Tun-Kyi, B. Homey, M. Gombert, O. Boyman, G. Burg, Y. J. Liu, and M. Gilliet. 2005. Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production. J Exp Med 202 (1):135–43.PubMedCrossRefGoogle Scholar
  68. Nograles, K. E., L. C. Zaba, A. Shemer, J. Fuentes-Duculan, I. Cardinale, T. Kikuchi, M. Ramon, R. Bergman, J. G. Krueger, and E. Guttman-Yassky. 2009. IL-22-producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells. J Allergy Clin Immunol 123 (6):1244–52 e2.Google Scholar
  69. Nograles, K.E., L. C. Zaba, E. Guttman-Yassky, J. Fuentes-Duculan, M. Suarez-Farinas, I. Cardinale, A. Khatcherian, J. Gonzalez, K.C. Pierson, T.R. White, C. Pensabene, I. Coats, I. Novitskaya, M. A. Lowes, and J.G. Krueger. 2008. Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways. Br J Dermatol 159 (5):1092–102.PubMedGoogle Scholar
  70. Nurieva, R., X. O. Yang, G. Martinez, Y. Zhang, A. D. Panopoulos, L. Ma, K. Schluns, Q. Tian, S. S. Watowich, A. M. Jetten, and C. Dong. 2007. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 448 (7152):480–3.PubMedCrossRefGoogle Scholar
  71. Papp, K. A., R. G. Langley, M. Lebwohl, G. G. Krueger, P. Szapary, N. Yeilding, C. Guzzo, M. C. Hsu, Y. Wang, S. Li, L. T. Dooley, and K. Reich. 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):1675–84.PubMedCrossRefGoogle Scholar
  72. Peric, M., S. Koglin, S. M. Kim, S. Morizane, R. Besch, J. C. Prinz, T. Ruzicka, R. L. Gallo, and J. Schauber. 2008. IL-17A enhances vitamin D3-induced expression of cathelicidin antimicrobial peptide in human keratinocytes. J Immunol 181 (12):8504–12.PubMedGoogle Scholar
  73. Puel, A., R. Doffinger, A. Natividad, M. Chrabieh, G. Barcenas-Morales, C. Picard, A. Cobat, M. Ouachee-Chardin, A. Toulon, J. Bustamante, S. Al-Muhsen, M. Al-Owain, P. D. Arkwright, C. Costigan,V. McConnell, A. J. Cant, M. Abinum, M. Polak, P. F. Bougneres, D. Kumararatne, L. LMarodi, A. Nahum, C. Roifman, S. Blanche, A. Fischer, C. Bodemer, L. Abel, D. Lilic, and J. L. Casanova. 2010. Autoantibodies against IL-17A, IL-17F and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I. J Exp Med 207 (2):291–7.Google Scholar
  74. Rioux, J. D., R. J. Xavier, K. D. Taylor, M. S. Silverberg, P. Goyette, A. Huett, T. Green, P. Kuballa, M. M. Barmada, L. W. Datta, Y. Y. Shugart, A. M. Griffiths, S. R. Targan, A. F. Ippoliti, E. J. Bernard, L. Mei, D. L. Nicolae, M. Regueiro, L. P. Schumm, A. H. Steinhart, J. I. Rotter, R. H. Duerr, J. H. Cho, M. J. Daly, and S. R. Brant. 2007. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet 39 (5):596–604.PubMedCrossRefGoogle Scholar
  75. Sa, S. M., P. A. Valdez, J. Wu, K. Jung, F. Zhong, L. Hall, I. Kasman, J. Winer, Z. Modrusan, D. M. Danilenko, and W. Ouyang. 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):2229–40.PubMedGoogle Scholar
  76. Sabat, R., S. Philipp, C. Hoflich, S. Kreutzer, E. Wallace, K. Asadullah, H. D. Volk, W. Sterry, and K. Wolk. 2007. Immunopathogenesis of psoriasis. Exp Dermatol 16 (10):779–98.PubMedCrossRefGoogle Scholar
  77. Spolski, R., and W. J. Leonard. 2008. Interleukin-21: basic biology and implications for cancer and autoimmunity. Annu Rev Immunol 26:57–79.PubMedCrossRefGoogle Scholar
  78. Stern, R. S., T. Nijsten, S. R. Feldman, D. J. Margolis, and T. Rolstad. 2004. Psoriasis is common, carries a substantial burden even when not extensive, and is associated with widespread treatment dissatisfaction. J Investig Dermatol Symp Proc 9 (2):136–9.PubMedCrossRefGoogle Scholar
  79. Szabo, S. K., C. Hammerberg, Y. Yoshida, Z. Bata-Csorgo, and K. D. Cooper. 1998. Identification and quantitation of interferon-gamma producing T cells in psoriatic lesions: localization to both CD4+ and CD8+ subsets. J Invest Dermatol 111 (6):1072–8.PubMedCrossRefGoogle Scholar
  80. Teraki, Y., A. Miyake, R. Takebayashi, and T. Shiohara. 2004. Homing receptor and chemokine receptor on intraepidermal T cells in psoriasis vulgaris. Clin Exp Dermatol 29 (6):658–63.PubMedCrossRefGoogle Scholar
  81. Teunissen, M. B., C. W. Koomen, R. de Waal Malefyt, E. A. Wierenga, and J. D. Bos. 1998. Interleukin-17 and interferon-gamma synergize in the enhancement of proinflammatory cytokine production by human keratinocytes. J Invest Dermatol 111 (4):645–9.PubMedCrossRefGoogle Scholar
  82. Toda, M., D. Y. Leung, S. Molet, M. Boguniewicz, R. Taha, P. Christodoulopoulos, T. Fukuda, J. A. Elias, and Q. A. Hamid. 2003. Polarized in vivo expression of IL-11 and IL-17 between acute and chronic skin lesions. J Allergy Clin Immunol 111 (4):875–81.PubMedCrossRefGoogle Scholar
  83. Toichi, E., G. Torres, T. S. McCormick, T. Chang, M. A. Mascelli, C. L. Kauffman, N. Aria, A. B. Gottlieb, D. E. Everitt, B. Frederick, C. E. Pendley, and K. D. Cooper. 2006. An anti-IL-12p40 antibody down-regulates type 1 cytokines, chemokines, and IL-12/IL-23 in psoriasis. J Immunol 177 (7):4917–26.PubMedGoogle Scholar
  84. Trifari, S., C. D. Kaplan, E. H. Tran, N. K. Crellin, and H. Spits. 2009. Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from T(H)-17, T(H)1 and T(H)2 cells. Nat Immunol 10 (8):864–71.PubMedCrossRefGoogle Scholar
  85. Volpe, E., M. Touzot, N. Servant, M. A. Marloie-Provost, P. Hupe, E. Barillot, and V. Soumelis. 2009. Multiparametric analysis of cytokine-driven human Th17 differentiation reveals a differential regulation of IL-17 and IL-22 production. Blood 114 (17):3610–4.PubMedCrossRefGoogle Scholar
  86. Watson, W., H. M. Cann, E. M. Farber, and M. L. Nall. 1972. The genetics of psoriasis. Arch Dermatol 105 (2):197–207.PubMedCrossRefGoogle Scholar
  87. Wei, L., A. Laurence, K. M. Elias, and J. J. O’Shea. 2007. IL-21 is produced by Th17 cells and drives IL-17 production in a STAT3-dependent manner. J Biol Chem 282 (48):34605–10.PubMedCrossRefGoogle Scholar
  88. Williams, R. C., A. W. McKenzie, J. H. Roger, and V. C. Joysey. 1976. HL-A antigens in patients with guttate psoriasis. Br J Dermatol 95 (2):163–7.PubMedCrossRefGoogle Scholar
  89. Wright, J. F., Y. Guo, A. Quazi, D. P. Luxenberg, F. Bennett, J. F. Ross, Y. Qiu, M. J. Whitters, K. N. Tomkinson, K. Dunussi-Joannopoulos, B. M. Carreno, M. Collins, and N. M. Wolfman. 2007. Identification of an interleukin 17F/17A heterodimer in activated human CD4+ T cells. J Biol Chem 282 (18):13447–55.PubMedCrossRefGoogle Scholar
  90. Zaba, L. C., I. Cardinale, P. Gilleaudeau, M. Sullivan-Whalen, M. Suarez Farinas, J. Fuentes-Duculan, I. Novitskaya, A. Khatcherian, M. J. Bluth, M. A. Lowes, and J. G. Krueger. 2007. Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses. J Exp Med 204 (13):3183–94.PubMedCrossRefGoogle Scholar
  91. Zaba, L. C., M. Suarez-Farinas, J. Fuentes-Duculan, K. E. Nograles, E. Guttman-Yassky, I. Cardinale, M. A. Lowes, and J. G. Krueger. 2009a. 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):1022–10 e1-395.Google Scholar
  92. Zaba, L.C., J. Fuentes-Duculan, N.J. Eungdamrong, M.V. Abello, I. Novitskaya, K.C. Pierson, J. Gonzalez, J.G. Krueger, and M.A. Lowes. 2009b. Psoriasis is characterized by accumulation of immunostimulatory and Th1/Th17 Cell-Polarizing Myeloid Dendritic Cells. J Invest Dermatol 129:79–88.PubMedCrossRefGoogle Scholar
  93. Zhao, Y., A. Balato, R. Fishelevich, A. Chapoval, D. L. Mann, and A. A. Gaspari. 2009. Th17/Tc17 infiltration and associated cytokine gene expression in elicitation phase of allergic contact dermatitis. Br J Dermatol 161 (6):1301–6.PubMedCrossRefGoogle Scholar
  94. Zheng, Y., D. M. Danilenko, P. Valdez, I. Kasman, J. Eastham-Anderson, J. Wu, and W. Ouyang. 2007. Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 445 (7128):648–51.PubMedCrossRefGoogle Scholar
  95. Zhou, L., Ivanov, II, R. Spolski, R. Min, K. Shenderov, T. Egawa, D. E. Levy, W. J. Leonard, and D. R. Littman. 2007. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 8 (9):967–74.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Kristine E. Nograles
  • Batya Davidovici
  • James G. Krueger
    • 1
  1. 1.Laboratory for Investigative DermatologyThe Rockefeller UniversityNew YorkUSA

Personalised recommendations