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Molecular pathophysiology of psoriasis and molecular targets of antipsoriatic therapy

Published online by Cambridge University Press:  14 December 2009

Emőke Rácz  and
Errol P. Prens
Emőke Rácz*
Affiliation:
Department of Dermatology and Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Errol P. Prens
Affiliation:
Department of Dermatology and Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
*
*Corresponding author: Emőke Rácz, Erasmus MC, University Medical Center, Department of Immunology/Dermatology, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Tel: +3110 7043430; Fax: +3110 7044731; E-mail: [email protected]
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Abstract

Psoriasis is a chronic inflammatory skin disease characterised by elevated red scaly plaques on specific body sites. Histologically, the plaques are defined by epidermal hyperplasia, epidermal and dermal infiltration by leukocytes, and changes in the dermal microvasculature. Differentiation and activation are disturbed in lesional psoriatic keratinocytes, and the pool of proliferating keratinocytes is increased, which is accompanied by enhanced production of proinflammatory cytokines, adhesion molecules and antimicrobial peptides. These changes in psoriatic keratinocytes are caused by altered expression of genes associated with epidermal differentiation, and by activation of signalling pathways involving signal transducer and activator of transcription 3 (STAT3), type I interferon (IFN) and mitogen-activated protein kinase (MAPK). The number of T cells, and myeloid and plasmacytoid dendritic cells (DCs) is markedly increased in psoriatic lesions. Myeloid DCs produce interleukin (IL)-23, tumour necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS), which are crucial cytokines in the pathogenesis of psoriasis. IL-23 stimulates the secretion of IL-22 by T helper 17 cells, and IL-22 induces epidermal hyperplasia. The crosstalk between keratinocytes and leukocytes via their proinflammatory cytokines creates the vicious circle of chronic skin inflammation seen in psoriasis. This suggests that optimal treatment of psoriasis needs to target pathogenic pathways in both leukocytes and keratinocytes.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 11 , July 2009 , e38
Copyright
Copyright © Cambridge University Press 2009

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References

References

1Schon, M.P. and Boehncke, W.H. (2005) Psoriasis. New England Journal of Medicine 352, 1899-1912Google Scholar
2Nijsten, T. et al. (2005) Traditional systemic treatments have not fully met the needs of psoriasis patients: results from a national survey. Journal of the American Academy of Dermatology 52, 434-444Google Scholar
3Fuchs, E. and Horsley, V. (2008) More than one way to skin. Genes and Development 22, 976-985Google Scholar
4Gallo, R.L. and Huttner, K.M. (1998) Antimicrobial peptides: an emerging concept in cutaneous biology. Journal of Investigative Dermatology 111, 739-743CrossRefGoogle ScholarPubMed
5Palmer, C.N. et al. (2006) Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nature Genetics 38, 441-446CrossRefGoogle Scholar
6Bernerd, F., Magnaldo, T. and Darmon, M. (1992) Delayed onset of epidermal differentiation in psoriasis. Journal of Investigative Dermatology 98, 902-910Google Scholar
7Bernard, B.A. et al. (1988) Abnormal sequence of expression of differentiation markers in psoriatic epidermis: inversion of two steps in the differentiation program? Journal of Investigative Dermatology 90, 801-805Google Scholar
8Ghadially, R., Reed, J.T. and Elias, P.M. (1996) Stratum corneum structure and function correlates with phenotype in psoriasis. Journal of Investigative Dermatology 107, 558-564CrossRefGoogle ScholarPubMed
9Thelu, J., Rossio, P. and Favier, B. (2002) Notch signalling is linked to epidermal cell differentiation level in basal cell carcinoma, psoriasis and wound healing. BMC Dermatology 2, 7Google Scholar
10Mossner, R. et al. (2004) Variations in the genes encoding the peroxisome proliferator-activated receptors alpha and gamma in psoriasis. Archives of Dermatological Research 296, 1-5Google Scholar
11Komine, M. et al. (2007) Early inflammatory changes in the "perilesional skin" of psoriatic plaques: is there interaction between dendritic cells and keratinocytes? Journal of Investigative Dermatology 127, 1915-1922Google Scholar
12King, L.E. Jr. et al. (1990) Epidermal growth factor/transforming growth factor alpha receptors and psoriasis. Journal of Investigative Dermatology 95, 10S-12SCrossRefGoogle ScholarPubMed
13Shen, C.S. et al. (2005) The expression of p63 during epidermal remodeling in psoriasis. Journal of Dermatology 32, 236-242Google Scholar
14Miura, H. et al. (2000) Involvement of insulin-like growth factor-I in psoriasis as a paracrine growth factor: dermal fibroblasts play a regulatory role in developing psoriatic lesions. Archives of Dermatological Research 292, 590-597CrossRefGoogle ScholarPubMed
15Elder, J.T. et al. (1990) Growth factor and proto-oncogene expression in psoriasis. Journal of Investigative Dermatology 95, 7S-9SGoogle Scholar
16Gaspari, A.A. (2006) Innate and adaptive immunity and the pathophysiology of psoriasis. Journal of the American Academy of Dermatology 54, S67-80CrossRefGoogle ScholarPubMed
17Bos, J.D. et al. (2005) Psoriasis: dysregulation of innate immunity. British Journal of Dermatology 152, 1098-1107Google Scholar
18Buchau, A.S. and Gallo, R.L. (2007) Innate immunity and antimicrobial defense systems in psoriasis. Clinics in Dermatology 25, 616-624CrossRefGoogle ScholarPubMed
19Hollox, E.J. et al. (2008) Psoriasis is associated with increased beta-defensin genomic copy number. Nature Genetics 40, 23-25Google Scholar
20van der Fits, L. et al. (2004) In psoriasis lesional skin the type I interferon signaling pathway is activated, whereas interferon-alpha sensitivity is unaltered. Journal of Investigative Dermatology 122, 51-60CrossRefGoogle ScholarPubMed
21Nestle, F.O. et al. (2005) Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production. Journal of Experimental Medicine 202, 135-143Google Scholar
22Cooper, K.D. et al. (1990) Interleukin-1 in human skin: dysregulation in psoriasis. Journal of Investigative Dermatology 95, 24S-26SGoogle Scholar
23Hertle, M.D. et al. (1992) Aberrant integrin expression during epidermal wound healing and in psoriatic epidermis. Journal of Clinical Investigation 89, 1892-1901CrossRefGoogle ScholarPubMed
24Nickoloff, B.J. et al. (2006) Lessons learned from psoriatic plaques concerning mechanisms of tissue repair, remodeling, and inflammation. Journal of Investigative Dermatology Symposium Proceedings 11, 16-29CrossRefGoogle ScholarPubMed
25Sano, S. et al. (1999) Keratinocyte-specific ablation of Stat3 exhibits impaired skin remodeling, but does not affect skin morphogenesis. EMBO Journal 18, 4657-4668Google Scholar
26Dauer, D.J. et al. (2005) Stat3 regulates genes common to both wound healing and cancer. Oncogene 24, 3397-3408CrossRefGoogle ScholarPubMed
27Sano, S. et al. (2005) Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. Nature Medicine 11, 43-49Google Scholar
28Johansen, C. et al. (2006) Protein expression of TNF-alpha in psoriatic skin is regulated at a posttranscriptional level by MAPK-activated protein kinase 2. Journal of Immunology 176, 1431-1438Google Scholar
29Funding, A.T. et al. (2007) Mitogen- and stress-activated protein kinase 2 and cyclic AMP response element binding protein are activated in lesional psoriatic epidermis. Journal of Investigative Dermatology 127, 2012-2019Google Scholar
30Haase, I. et al. (2001) A role for mitogen-activated protein kinase activation by integrins in the pathogenesis of psoriasis. Journal of Clinical Investigation 108, 527-536Google Scholar
31Otkjaer, K. et al. (2007) IL-20 gene expression is induced by IL-1beta through mitogen-activated protein kinase and NF-kappaB-dependent mechanisms. Journal of Investigative Dermatology 127, 1326-1336CrossRefGoogle ScholarPubMed
32Otkjaer, K. et al. (2005) The dynamics of gene expression of interleukin-19 and interleukin-20 and their receptors in psoriasis. British Journal of Dermatology 153, 911-918CrossRefGoogle ScholarPubMed
33Wolk, K. et al. (2009) IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-gamma are not. Journal of Molecular Medicine 87, 523-536CrossRefGoogle ScholarPubMed
34de Cid, R. et al. (2009) Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis. Nature Genetics 41, 211-215Google Scholar
35Zhang, X.J. et al. (2009) Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21. Nature Genetics 41, 205-210Google Scholar
36Stratis, A. et al. (2006) Pathogenic role for skin macrophages in a mouse model of keratinocyte-induced psoriasis-like skin inflammation. Journal of Clinical Investigation 116, 2094-2104CrossRefGoogle Scholar
37Pasparakis, M. et al. (2002) TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2. Nature 417, 861-866Google Scholar
38Xia, Y.P. et al. (2003) Transgenic delivery of VEGF to mouse skin leads to an inflammatory condition resembling human psoriasis. Blood 102, 161-168Google Scholar
39Boyman, O. et al. (2004) Spontaneous development of psoriasis in a new animal model shows an essential role for resident T cells and tumor necrosis factor-alpha. Journal of Experimental Medicine 199, 731-736Google Scholar
40Wrone-Smith, T. and Nickoloff, B.J. (1996) Dermal injection of immunocytes induces psoriasis. Journal of Clinical Investigation 98, 1878-1887Google Scholar
41Bos, J. et al. (1983) Immunocompetent cells in psoriasis. In situ immunophenotyping by monoclonal antibodies. Archives of Dermatological Research 275, 181-189Google Scholar
42Zaba, L.C. et al. (2009) Psoriasis is characterized by accumulation of immunostimulatory and Th1/Th17 cell-polarizing myeloid dendritic cells. Journal of Investigative Dermatology 129, 79-88CrossRefGoogle ScholarPubMed
43Cumberbatch, M. et al. (2006) Impaired Langerhans cell migration in psoriasis. Journal of Experimental Medicine 203, 953-960Google Scholar
44Beurskens, T. et al. (1989) Epidermal proliferation and accumulation of polymorphonuclear leukocytes in the psoriatic lesion. Dermatologica 178, 67-72CrossRefGoogle ScholarPubMed
45van de Kerkhof, P.C. and Lammers, A.M. (1987) Intraepidermal accumulation of polymorphonuclear leukocytes in chronic stable plaque psoriasis. Dermatologica 174, 224-227CrossRefGoogle ScholarPubMed
46Wolk, K. et al. (2004) IL-22 increases the innate immunity of tissues. Immunity 21, 241-254Google Scholar
47Uyemura, K. et al. (1993) The cytokine network in lesional and lesion-free psoriatic skin is characterized by a T-helper type 1 cell-mediated response. Journal of Investigative Dermatology 101, 701-705Google Scholar
48Lee, E. et al. (2004) Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. Journal of Experimental Medicine 199, 125-130CrossRefGoogle ScholarPubMed
49Johansen, C. et al. (2009) Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin. British Journal of Dermatology 160, 319-324Google Scholar
50Zaba, L.C., Krueger, J.G. and Lowes, M.A. (2009) Resident and "inflammatory" dendritic cells in human skin. Journal of Investigative Dermatology 129, 302-308CrossRefGoogle ScholarPubMed
51Wollenberg, A. et al. (2002) Plasmacytoid dendritic cells: a new cutaneous dendritic cell subset with distinct role in inflammatory skin diseases. Journal of Investigative Dermatology 119, 1096-1102Google Scholar
52Downs, A.M. and Dunnill, M.G. (2000) Exacerbation of psoriasis by interferon-alpha therapy for hepatitis C. Clinical and Experimental Dermatology 25, 351-352CrossRefGoogle ScholarPubMed
53Funk, J. et al. (1991) Psoriasis induced by interferon-alpha. British Journal of Dermatology 125, 463-465Google Scholar
54Ketikoglou, I. et al. (2005) Extensive psoriasis induced by pegylated interferon alpha-2b treatment for chronic hepatitis B. European Journal of Dermatology 15, 107-109Google Scholar
55Pauluzzi, P. et al. (1993) Psoriasis exacerbation induced by interferon-alpha. Report of two cases. Acta Dermato-Venereologica 73, 395Google Scholar
56Lande, R. et al. (2007) Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 449, 564-569Google Scholar
57Zaba, L.C. et al. (2007) Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses. Journal of Experimental Medicine 204, 3183-3194Google Scholar
58Lowes, M.A. et al. (2005) Increase in TNF-alpha and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a). Proceedings of the National Academy of Sciences of the United States of America 102, 19057-19062Google Scholar
59Wang, F. et al. (2006) Prominent production of IL-20 by CD68 +/CD11c+ myeloid-derived cells in psoriasis: Gene regulation and cellular effects. Journal of Investigative Dermatology 126, 1590-1599Google Scholar
60Clark, R. et al. (2006) The vast majority of CLA+ T cells are resident in normal skin. Journal of Immunology 176, 4431-4439CrossRefGoogle ScholarPubMed
61Albanesi, C., De Pita, O. and Girolomoni, G. (2007) Resident skin cells in psoriasis: a special look at the pathogenetic functions of keratinocytes. Clinics in Dermatology 25, 581-588Google Scholar
62Nair, R., Stuart, P. and Nistor, I. (2006) Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene. American Journal of Human Genetics 78, 827-851Google Scholar
63Eedy, D.J. et al. (1990) Clearance of severe psoriasis after allogenic bone marrow transplantation. British Medical Journal 300, 908CrossRefGoogle ScholarPubMed
64Gardembas-Pain, M. et al. (1990) Psoriasis after allogeneic bone marrow transplantation. Archives of Dermatology 126, 1523CrossRefGoogle ScholarPubMed
65Johnston, A. et al. (2004) Peripheral blood T cell responses to keratin peptides that share sequences with streptococcal M proteins are largely restricted to skin-homing CD8(+) T cells. Clinical and Experimental Immunology 138, 83-93Google Scholar
66Skov, L. and Baadsgaard, O. (1995) Superantigens. Do they have a role in skin diseases? Archives of Dermatology 131, 829-832Google Scholar
67Travers, J.B. et al. (1999) Epidermal HLA-DR and the enhancement of cutaneous reactivity to superantigenic toxins in psoriasis. Journal of Clinical Investigation 104, 1181-1189Google Scholar
68Lin, W.J. et al. (2001) Oligoclonal expansion of intraepidermal T cells in psoriasis skin lesions. Journal of Investigative Dermatology 117, 1546-1553Google Scholar
69Prinz, J.C. et al. (1999) Selection of conserved TCR VDJ rearrangements in chronic psoriatic plaques indicates a common antigen in psoriasis vulgaris. European Journal of Immunology 29, 3360-3368Google Scholar
70Lowes, M.A. et al. (2008) Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. Journal of Investigative Dermatology 128, 1207-1211Google Scholar
71Pene, J. et al. (2008) Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes. Journal of Immunology 180, 7423-7430Google Scholar
72Kryczek, I. et al. (2008) Induction of IL-17+ T cell trafficking and development by IFN-gamma: mechanism and pathological relevance in psoriasis. Journal of Immunology 181, 4733-4741Google Scholar
73Sugiyama, H. et al. (2005) Dysfunctional blood and target tissue CD4 + CD25high regulatory T cells in psoriasis: mechanism underlying unrestrained pathogenic effector T cell proliferation. Journal of Immunology 174, 164-173CrossRefGoogle ScholarPubMed
74Boehncke, W. et al. (1995) A subset of macrophages located along the basement membrane (“lining cells”) is a characteristic histopathological feature of psoriasis. American Journal of Dermatopathology. 17, 139-144Google Scholar
75Wang, H. et al. (2006) Activated macrophages are essential in a murine model for T cell-mediated chronic psoriasiform skin inflammation. Journal of Clinical Investigation 116, 2105-2114Google Scholar
76Lowes, M.A., Bowcock, A.M. and Krueger, J.G. (2007) Pathogenesis and therapy of psoriasis. Nature 445, 866-873Google Scholar
77Homey, B. and Meller, S. (2008) Chemokines and other mediators as therapeutic targets in psoriasis vulgaris. Clinics in Dermatology 26, 539-545CrossRefGoogle ScholarPubMed
78Homey, B. et al. (2002) CCL27-CCR10 interactions regulate T cell-mediated skin inflammation. Nature Medicine 8, 157-165Google Scholar
79Nomura, I. et al. (2003) Distinct patterns of gene expression in the skin lesions of atopic dermatitis and psoriasis: a gene microarray analysis. Journal of Allergy and Clinical Immunology 112, 1195-1202Google Scholar
80Caruso, R. et al. (2009) Involvement of interleukin-21 in the epidermal hyperplasia of psoriasis. Nature Medicine 15, 1013-1015Google Scholar
81Wolk, K. et al. (2006) IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. European Journal of Immunology 36, 1309-1323Google Scholar
82Sa, S.M. 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. Journal of Immunology 178, 2229-2240Google Scholar
83Nograles, K.E. et al. (2008) Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways. British Journal of Dermatology 159, 1092-1102Google Scholar
84Wei, L. et al. (1999) IL-1 beta and IFN-gamma induce the regenerative epidermal phenotype of psoriasis in the transwell skin organ culture system. IFN-gamma up-regulates the expression of keratin 17 and keratinocyte transglutaminase via endogenous IL-1 production. Journal of Pathology 187, 358-364Google Scholar
85Blauvelt, A. (2008) T-helper 17 cells in psoriatic plaques and additional genetic links between IL-23 and psoriasis. Journal of Investigative Dermatology 128, 1064-1067Google Scholar
86Piskin, G. et al. (2006) 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 176, 1908-1915CrossRefGoogle ScholarPubMed
87Cargill, M. et al. (2007) A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. American Journal of Human Genetics 80, 273-290Google Scholar
88Nair, R.P. et al. (2008) Polymorphisms of the IL12B and IL23R genes are associated with psoriasis. Journal of Investigative Dermatology 128, 1653-1661Google Scholar
89Garcia, V.E. et al. (2008) Detailed genetic characterization of the interleukin-23 receptor in psoriasis. Genes and Immunity 9, 546-555Google Scholar
90Krueger, G.G. et al. (2007) A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis. New England Journal of Medicine 356, 580-592Google Scholar
91van der Fits, L. et al. (2009) Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. Journal of Immunology 182, 5836-5845CrossRefGoogle ScholarPubMed
92Haider, A.S. 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. Journal of Immunology 180, 1913-1920Google Scholar
93Haider, A.S. et al. (2008) Insights into gene modulation by therapeutic TNF and IFNgamma antibodies: TNF regulates IFNgamma production by T cells and TNF-regulated genes linked to psoriasis transcriptome. Journal of Investigative Dermatology 128, 655-666Google Scholar
94Tracey, D. et al. (2008) Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacology and Therapeutics 117, 244-279Google Scholar
95Nair, R.P. et al. (2009) Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nature Genetics 41, 199-204Google Scholar
96Chang, M. et al. (2008) Variants in the 5q31 cytokine gene cluster are associated with psoriasis. Genes and Immunity 9, 176-181Google Scholar
97Costa, C., Incio, J. and Soares, R. (2007) Angiogenesis and chronic inflammation: cause or consequence? Angiogenesis 10, 149-166Google Scholar
98Detmar, M. (2004) Evidence for vascular endothelial growth factor (VEGF) as a modifier gene in psoriasis. Journal of Investigative Dermatology 122, xiv-xvGoogle Scholar
99Katugampola, G.A., Rees, A.M. and Lanigan, S.W. (1995) Laser treatment of psoriasis. British Journal of Dermatology 133, 909-913Google Scholar
100Ros, A.M. et al. (1996) Psoriasis response to the pulsed dye laser. Lasers in Surgery and Medicine 19, 331-335Google Scholar
101Hern, S. et al. (2001) Immunohistochemical evaluation of psoriatic plaques following selective photothermolysis of the superficial capillaries. British Journal of Dermatology 145, 45-53CrossRefGoogle ScholarPubMed
102Zelickson, B.D. et al. (1996) Clinical and histologic evaluation of psoriatic plaques treated with a flashlamp pulsed dye laser. Journal of the American Academy of Dermatology 35, 64-68Google Scholar
103Ehrlich, A. et al. (2004) Micellar paclitaxel improves severe psoriasis in a prospective phase II pilot study. Journal of the American Academy of Dermatology 50, 533-540Google Scholar
104Sauder, D. et al. (2002) Neovastat (AE-941), an inhibitor of angiogenesis: Randomized phase I/II clinical trial results in patients with plaque psoriasis. Journal of the American Academy of Dermatology 47, 535-541Google Scholar
105Halin, C. et al. (2008) Inhibition of chronic and acute skin inflammation by treatment with a vascular endothelial growth factor receptor tyrosine kinase inhibitor. American Journal of Pathology 173, 265-277CrossRefGoogle ScholarPubMed
106Bowcock, A.M. et al. (2001) Insights into psoriasis and other inflammatory diseases from large-scale gene expression studies. Human Molecular Genetics 10, 1793-1805Google Scholar
107Oestreicher, J.L. et al. (2001) Molecular classification of psoriasis disease-associated genes through pharmacogenomic expression profiling. Pharmacogenomics Journal 1, 272-287Google Scholar
108Zhou, X. et al. (2003) Novel mechanisms of T-cell and dendritic cell activation revealed by profiling of psoriasis on the 63,100-element oligonucleotide array. Physiological Genomics 13, 69-78CrossRefGoogle ScholarPubMed
109Kulski, J.K. et al. (2005) Gene expression profiling of Japanese psoriatic skin reveals an increased activity in molecular stress and immune response signals. Journal of Molecular Medicine 83, 964-975CrossRefGoogle ScholarPubMed
110Reischl, J. et al. (2007) Increased expression of Wnt5a in psoriatic plaques. Journal of Investigative Dermatology 127, 163-169Google Scholar
111Yao, Y. et al. (2008) Type I interferon: potential therapeutic target for psoriasis? PLoS ONE 3, e2737Google Scholar
112Quekenborn-Trinquet, V. et al. (2005) Gene expression profiles in psoriasis: analysis of impact of body site location and clinical severity. British Journal of Dermatology 152, 489-504Google Scholar
113Gudjonsson, J.E. et al. (2009) Global gene expression analysis reveals evidence for decreased lipid biosynthesis and increased innate immunity in uninvolved psoriatic skin. Journal of Investigative Dermatology 129, 2795-2804Google Scholar
114Guttman-Yassky, E. et al. (2007) Major differences in inflammatory dendritic cells and their products distinguish atopic dermatitis from psoriasis. Journal of Allergy and Clinical Immunology 119, 1210-1217Google Scholar
115Ito, M. et al. (2004) Gene expression of enzymes for tryptophan degradation pathway is upregulated in the skin lesions of patients with atopic dermatitis or psoriasis. Journal of Dermatological Science 36, 157-164Google Scholar
116de Jongh, G.J. et al. (2005) High expression levels of keratinocyte antimicrobial proteins in psoriasis compared with atopic dermatitis. Journal of Investigative Dermatology 125, 1163-1173Google Scholar
117Wenzel, J. et al. (2008) Gene expression profiling of lichen planus reflects CXCL9+-mediated inflammation and distinguishes this disease from atopic dermatitis and psoriasis. Journal of Investigative Dermatology 128, 67-78Google Scholar
118Haider, A.S. et al. (2007) Novel insight into the agonistic mechanism of alefacept in vivo: differentially expressed genes may serve as biomarkers of response in psoriasis patients. Journal of Immunology 178, 7442-7449CrossRefGoogle ScholarPubMed
119Hochberg, M. et al. (2007) Genomic-scale analysis of psoriatic skin reveals differentially expressed insulin-like growth factor-binding protein-7 after phototherapy. British Journal of Dermatology 156, 289-300Google Scholar
120Koczan, D. et al. (2005) Gene expression profiling of peripheral blood mononuclear leukocytes from psoriasis patients identifies new immune regulatory molecules. European Journal of Dermatology 15, 251-257Google Scholar
121Jung, M. et al. (2004) Expression profiling of IL-10-regulated genes in human monocytes and peripheral blood mononuclear cells from psoriatic patients during IL-10 therapy. European Journal of Immunology 34, 481-493Google Scholar
122Haider, A.S. et al. (2008) Cellular Genomic Maps Help Dissect Pathology in Human Skin Disease. Journal of Investigative Dermatology 128, 606-615Google Scholar
123Mee, J.B. et al. (2006) Interleukin-1: a key inflammatory mediator in psoriasis? Cytokine 33, 72-78Google Scholar
124Mee, J.B. et al. (2007) The psoriatic transcriptome closely resembles that induced by interleukin-1 in cultured keratinocytes: dominance of innate immune responses in psoriasis. American Journal of Pathology 171, 32-42Google Scholar
125Haider, A.S. et al. (2006) Genomic analysis defines a cancer-specific gene expression signature for human squamous cell carcinoma and distinguishes malignant hyperproliferation from benign hyperplasia. Journal of Investigative Dermatology 126, 869-881Google Scholar
126Stojadinovic, O. et al. (2007) Novel genomic effects of glucocorticoids in epidermal keratinocytes: inhibition of apoptosis, interferon-gamma pathway, and wound healing along with promotion of terminal differentiation. Journal of Biological Chemistry 282, 4021-4034Google Scholar
127Chamian, F. et al. (2005) Alefacept reduces infiltrating T cells, activated dendritic cells, and inflammatory genes in psoriasis vulgaris. Proceedings of the National Academy of Sciences of the United States of America 102, 2075-2080Google Scholar
128Haider, A.S. et al. (2007) Insights into Gene Modulation by Therapeutic TNF and IFNgamma Antibodies: TNF Regulates IFNgamma Production by T Cells and TNF-Regulated Genes Linked to Psoriasis Transcriptome. Journal of Investigative Dermatology 128, 655-666Google Scholar
129Haider, A.S. et al. (2007) Effects of etanercept are distinct from infliximab in modulating proinflammatory genes in activated human leukocytes. Journal of Investigative Dermatology. Symposium Proceedings 12, 9-15CrossRefGoogle ScholarPubMed
130Malaviya, R. et al. (2006) Etanercept induces apoptosis of dermal dendritic cells in psoriatic plaques of responding patients. Journal of the American Academy of Dermatology 55, 590-597CrossRefGoogle ScholarPubMed
131Rozenblit, M. and Lebwohl, M. (2009) New biologics for psoriasis and psoriatic arthritis. Dermatological Therapy 22, 56-60Google Scholar
132Papp, K.A. 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, 1675-1684CrossRefGoogle ScholarPubMed
133Leonardi, C.L. 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, 1665-1674Google Scholar
134Reich, K., Yasothan, U. and Kirkpatrick, P. (2009) Ustekinumab. Nature Reviews. Drug Discovery 8, 355-356Google Scholar
135Kimball, A.B. et al. (2008) 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 144, 200-207Google Scholar
136Schmitt, J. et al. (2008) Efficacy and tolerability of biologic and nonbiologic systemic treatments for moderate-to-severe psoriasis: meta-analysis of randomized controlled trials. British Journal of Dermatology 159, 513-526Google Scholar
137Mittal, R. et al. (2009) Efficacy and safety of combination Acitretin and Pioglitazone therapy in patients with moderate to severe chronic plaque-type psoriasis: a randomized, double-blind, placebo-controlled clinical trial. Archives of Dermatology 145, 387-393Google Scholar
138Murase, J.E. et al. (2005) Hormonal effect on psoriasis in pregnancy and post partum. Archives of Dermatology 141, 601-606Google Scholar
139Sterry, W. et al. (2009) Immunosuppressive therapy in dermatology and PML. Journal der Deutschen Dermatologischen Gesellschaft (Journal of the German Society of Dermatology) 7, 5Google Scholar

Further reading, resources and contacts

The Medline Plus website is a service of the US National Library of Medicine and the National Institutes of Health, and provides information on various skin conditions:

http://www.nlm.nih.gov/medlineplus/skinconditions.html

The American Academy of Dermatology is the main body representing dermatologists in the USA and provides an extensive resource for public education on diseases of the skin:

http://www.aad.org/

The International Psoriasis Council has created a forum for psoriasis experts and health professionals to share knowledge, experiences and insights towards optimising our understanding and treatment of psoriasis.

http://www.psoriasiscouncil.org/

The National Psoriasis Foundation provides an up-to-date website with practical information for patients, doctors and researchers on current psoriasis drugs, research projects funded etc.

http://www.psoriasis.org

Nestle, F.O. et al. (2009) Psoriasis. New England Journal of Medicine 361, 496-509Google Scholar
Annunziato, F. et al. (2009) Type 17 T helper cells – origins, features and possible roles in rheumatic disease. Nature Reviews Rheumatology 5, 325-331Google Scholar
Elder, J.T. (2009) Genome-wide association scan yields new insights into the immunopathogenesis of psoriasis. Genes and Immunity 10, 201-209Google Scholar
Nestle, F.O. et al. (2009) Psoriasis. New England Journal of Medicine 361, 496-509Google Scholar
Annunziato, F. et al. (2009) Type 17 T helper cells – origins, features and possible roles in rheumatic disease. Nature Reviews Rheumatology 5, 325-331Google Scholar
Elder, J.T. (2009) Genome-wide association scan yields new insights into the immunopathogenesis of psoriasis. Genes and Immunity 10, 201-209Google Scholar