The immunological and genetic aspects in psoriasis

Psoriasis is a chronic and immune-mediated inflammatory skin disorder associated with complex genetic susceptibility. Studies focused on the immunological mechanism have revealed innate and adaptive immune activation in psoriatic lesions, including large numbers of immune cells activated to produce many cytokines, chemokines, and other inflammatory molecules. Knowledge on the genetic basis of psoriasis highlights genetic susceptibility factors that play a crucial role in regulation of immunity, epidermal proliferation, and skin barrier formation. Genetic susceptibility factors affecting both the immune system and epidermis could predispose to disease. Herein, we review the current knowledge on the role of genetic and immunological factors in the development of psoriasis.

[1]  Sally Attia,et al.  Epidermal Differentiation Complex , 2010 .

[2]  M. Madsen,et al.  Mitogen- and stress-activated protein kinase 1 is activated in lesional psoriatic epidermis and regulates the expression of pro-inflammatory cytokines. , 2006, The Journal of investigative dermatology.

[3]  A. Bowcock,et al.  The genetics of psoriasis: a complex disorder of the skin and immune system. , 1998, Human molecular genetics.

[4]  James T. Elder,et al.  Multiple Loci within the Major Histocompatibility Complex Confer Risk of Psoriasis , 2009, PLoS genetics.

[5]  W. Jochum,et al.  T cells involved in psoriasis vulgaris belong to the Th1 subset. , 1994, The Journal of investigative dermatology.

[6]  Lisa C. Zaba,et al.  Th17 cytokines interleukin (IL)‐17 and IL‐22 modulate distinct inflammatory and keratinocyte‐response pathways , 2008, The British journal of dermatology.

[7]  B. Thiers.  Pathogenesis and clinical features of psoriasis , 2008 .

[8]  Alkes L. Price,et al.  New approaches to population stratification in genome-wide association studies , 2010, Nature Reviews Genetics.

[9]  Matti Pirinen,et al.  Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity , 2012 .

[10]  A. Kimball,et al.  The burden of autoimmune disease: a comparison of prevalence ratios in patients with psoriatic arthritis and psoriasis. , 2009, Journal of the American Academy of Dermatology.

[11]  Scott F. Saccone,et al.  A Genome-Wide Association Study of Psoriasis and Psoriatic Arthritis Identifies New Disease Loci , 2008, PLoS genetics.

[12]  E. Christophers,et al.  Psoriasis of early and late onset: characterization of two types of psoriasis vulgaris. , 1985, Journal of the American Academy of Dermatology.

[13]  V. Álvarez,et al.  New psoriasis susceptibility genes: momentum for skin-barrier disruption. , 2011, The Journal of investigative dermatology.

[14]  L. Fouser,et al.  Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides , 2006, The Journal of experimental medicine.

[15]  Christian Gieger,et al.  Genome-wide association analysis identifies three psoriasis susceptibility loci , 2010, Nature Genetics.

[16]  R. Trembath,et al.  Family-based analysis using a dense single-nucleotide polymorphism-based map defines genetic variation at PSORS1, the major psoriasis-susceptibility locus. , 2002, American journal of human genetics.

[17]  Liangdan Sun,et al.  Identification of a missense variant in LNPEP that confers psoriasis risk. , 2014, The Journal of investigative dermatology.

[18]  A. Magener,et al.  Characterisation of psoriasis susceptibility locus 6 (PSORS6) in patients with early onset psoriasis and evidence for interaction with PSORS1 , 2009, Journal of Medical Genetics.

[19]  A. Gottlieb,et al.  Differential Expression of Phosphorylated NF-κB/RelA in Normal and Psoriatic Epidermis and Downregulation of NF-κB in Response to Treatment with Etanercept , 2005 .

[20]  F. Morel,et al.  A role for T cell‐derived interleukin 22 in psoriatic skin inflammation , 2007, Clinical and experimental immunology.

[21]  L. Herrinton,et al.  The association of psoriasis with autoimmune diseases. , 2012, Journal of the American Academy of Dermatology.

[22]  James G. Krueger,et al.  Pathogenesis and therapy of psoriasis , 2007, Nature.

[23]  S. Kaesler,et al.  CXCL16 and CXCR6 are upregulated in psoriasis and mediate cutaneous recruitment of human CD8+ T cells. , 2012, The Journal of investigative dermatology.

[24]  N. J. Eungdamrong,et al.  Psoriasis is characterized by accumulation of immunostimulatory and Th1/Th17 cell-polarizing myeloid dendritic cells. , 2009, The Journal of investigative dermatology.

[25]  A. Bowcock,et al.  Psoriasis vulgaris: cutaneous lymphoid tissue supports T-cell activation and "Type 1" inflammatory gene expression. , 2004, Trends in immunology.

[26]  K. Asadullah,et al.  Flow cytometric characterization of lesional T cells in psoriasis: intracellular cytokine and surface antigen expression indicates an activated, memory/effector type 1 immunophenotype , 2000, Archives of Dermatological Research.

[27]  Pui-Yan Kwok,et al.  Genomewide Scan Reveals Association of Psoriasis with IL-23 and NF-κB Pathways , 2008, Nature Genetics.

[28]  B. Kirby,et al.  TNFα Inhibitors in the Treatment of Psoriasis and Psoriatic Arthritis , 2012, BioDrugs.

[29]  D. Wallach,et al.  Elevated tumour necrosis factor‐alpha (TNF‐α) biological activity in psoriatic skin lesions , 1994, Clinical and experimental immunology.

[30]  John BowesRobert.  Rare variation at the TNFAIP3 locus and susceptibility to rheumatoid arthritis , 2010 .

[31]  Christian Gieger,et al.  Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis , 2010, Nature Genetics.

[32]  Wei Huang,et al.  Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21 , 2009, Nature Genetics.

[33]  W. Mueller,et al.  Cyclosporin A for psoriasis. , 1979, The New England journal of medicine.

[34]  J. Renauld,et al.  IL-22 Is Required for Imiquimod-Induced Psoriasiform Skin Inflammation in Mice , 2011, The Journal of Immunology.

[35]  A. Bowcock,et al.  Psoriasis: genetic associations and immune system changes , 2007, Genes and Immunity.

[36]  V. Kuchroo,et al.  Interleukin-17 and type 17 helper T cells. , 2009, The New England journal of medicine.

[37]  H. Spits,et al.  Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from TH-17, TH1 and TH2 cells , 2009, Nature Immunology.

[38]  C. Johansen,et al.  Mitogen- and stress-activated protein kinase 2 and cyclic AMP response element binding protein are activated in lesional psoriatic epidermis. , 2007, The Journal of investigative dermatology.

[39]  F. Nestle,et al.  The IL-23/Th17 axis in the immunopathogenesis of psoriasis. , 2009, The Journal of investigative dermatology.

[40]  A. Bowcock,et al.  PSORS2 is due to mutations in CARD14. , 2012, American Journal of Human Genetics.

[41]  Richard C Trembath,et al.  Identification of ZNF313/RNF114 as a novel psoriasis susceptibility gene. , 2008, Human molecular genetics.

[42]  Lisa C. Zaba,et al.  Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. , 2008, The Journal of investigative dermatology.

[43]  G. T. te Meerman,et al.  Evaluation of the IRF-2 gene as a candidate for PSORS3. , 2004, The Journal of investigative dermatology.

[44]  Raquel Soares,et al.  Angiogenesis and chronic inflammation: cause or consequence? , 2007, Angiogenesis.

[45]  I. Marenholz,et al.  Genes encoding structural proteins of epidermal cornification and S100 calcium-binding proteins form a gene complex ("epidermal differentiation complex") on human chromosome 1q21. , 1996, The Journal of investigative dermatology.

[46]  J. Catanese,et al.  The autoimmune disease-associated IL12B and IL23R polymorphisms in multiple sclerosis. , 2007, Human immunology.

[47]  W. Boehncke,et al.  Animal models of psoriasis. , 2007, Clinics in dermatology.

[48]  Liangdan Sun,et al.  Polymorphisms in interleukin-15 gene on chromosome 4q31.2 are associated with psoriasis vulgaris in Chinese population. , 2007, The Journal of investigative dermatology.

[49]  T. Wienker,et al.  Genomewide scan in german families reveals evidence for a novel psoriasis-susceptibility locus on chromosome 19p13. , 2000, American journal of human genetics.

[50]  A. Reis,et al.  Systematic linkage disequilibrium analysis of SLC12A8 at PSORS5 confirms a role in susceptibility to psoriasis vulgaris. , 2005, The Journal of investigative dermatology.

[51]  K. Scharffetter-Kochanek,et al.  Key role of macrophages in the pathogenesis of CD18 hypomorphic murine model of psoriasis. , 2009, The Journal of investigative dermatology.

[52]  James T. Elder,et al.  Evidence for two psoriasis susceptibility loci (HLA and 17q) and two novel candidate regions (16q and 20p) by genome-wide scan. , 1997, Human molecular genetics.

[53]  Stefan Jenisch,et al.  Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene. , 2006, American journal of human genetics.

[54]  A. Bowcock,et al.  Getting under the skin: the immunogenetics of psoriasis , 2005, Nature Reviews Immunology.

[55]  B. Kamińska,et al.  Targeting signaling pathways with small molecules to treat autoimmune disorders , 2008, Expert review of clinical immunology.

[56]  Christian Gieger,et al.  Genome-wide association study identifies a psoriasis susceptibility locus at TRAF3IP2 , 2010, Nature Genetics.

[57]  Jinhua Xu,et al.  Transcriptional regulatory network for psoriasis , 2013, The Journal of dermatology.

[58]  F. Nestle,et al.  Characterization of dermal dendritic cells in psoriasis. Autostimulation of T lymphocytes and induction of Th1 type cytokines. , 1994, The Journal of clinical investigation.

[59]  Wei Li,et al.  Follow-up analysis of PSORS9 in 151 Chinese families confirmed the linkage to 4q31-32 and refined the evidence to the families of early-onset psoriasis. , 2007, The Journal of investigative dermatology.

[60]  J. Riley,et al.  Psoriasis susceptibility locus in chromosome region 3q21 identified in patients from southwest Sweden , 1999, European Journal of Human Genetics.

[61]  Jun Yan,et al.  New insights of T cells in the pathogenesis of psoriasis , 2012, Cellular and Molecular Immunology.

[62]  M. Yamamura,et al.  The cytokine network in lesional and lesion-free psoriatic skin is characterized by a T-helper type 1 cell-mediated response. , 1993, The Journal of investigative dermatology.

[63]  A. Gottlieb,et al.  Differential expression of phosphorylated NF-kappaB/RelA in normal and psoriatic epidermis and downregulation of NF-kappaB in response to treatment with etanercept. , 2005, The Journal of investigative dermatology.

[64]  F. Nestle,et al.  Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities. , 2004, The Journal of clinical investigation.

[65]  Mark Lebwohl,et al.  Psoriasis , 1906, The Lancet.

[66]  N. Rose.  Autoimmune diseases. , 1981, Scientific American.

[67]  B. Kirby,et al.  TNF alpha inhibitors in the treatment of psoriasis and psoriatic arthritis. , 2005, BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy.

[68]  Xuejun Zhang,et al.  Association of HLA class I alleles with psoriasis vulgaris in southeastern Chinese Hans. , 2003, Journal of dermatological science.

[69]  K. Nakajima.  Critical role of the interleukin‐23//T‐helper 17 cell axis in the pathogenesis of psoriasis , 2012, The Journal of dermatology.

[70]  J. Todd,et al.  Analysis of 17 autoimmune disease-associated variants in type 1 diabetes identifies 6q23/TNFAIP3 as a susceptibility locus , 2009, Genes and Immunity.

[71]  P. Valdez,et al.  Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis , 2007, Nature.

[72]  O. Boyman,et al.  Plasmacytoid predendritic cells initiate psoriasis through interferon-α production , 2005, The Journal of experimental medicine.

[73]  O. Lunov,et al.  Targeting NF-κB with a Natural Triterpenoid Alleviates Skin Inflammation in a Mouse Model of Psoriasis1 , 2009, The Journal of Immunology.

[74]  L. Samuelsson,et al.  Association analysis of cystatin A and zinc finger protein 148, two genes located at the psoriasis susceptibility locus PSORS5. , 2004, The Journal of investigative dermatology.

[75]  J. Carucci,et al.  Human Langerhans cells induce distinct IL-22-producing CD4+ T cells lacking IL-17 production , 2009, Proceedings of the National Academy of Sciences.

[76]  E. Fisher,et al.  Evidence that a locus for familial psoriasis maps to chromosome 4q , 1996, Nature Genetics.

[77]  C. Albanesi,et al.  Keratinocytes in inflammatory skin diseases. , 2005, Current drug targets. Inflammation and allergy.

[78]  R. Clark,et al.  Misbehaving macrophages in the pathogenesis of psoriasis. , 2006, The Journal of clinical investigation.

[79]  Steven J. Schrodi,et al.  A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. , 2007, American journal of human genetics.

[80]  Gang Wang,et al.  IL-17A upregulates keratin 17 expression in keratinocytes through STAT1- and STAT3-dependent mechanisms. , 2011, The Journal of investigative dermatology.

[81]  H. Young,et al.  Impaired Langerhans cell migration in psoriasis , 2006, The Journal of experimental medicine.

[82]  James T. Elder.  PSORS1: linking genetics and immunology. , 2006, The Journal of investigative dermatology.

[83]  R. Trembath,et al.  Identification of a novel psoriasis susceptibility locus at 1p and evidence of epistasis between PSORS1 and candidate loci , 2001, Journal of medical genetics.

[84]  A. Gottlieb,et al.  NF-κB: an essential transcription factor in psoriasis. , 2013, Journal of dermatological science.

[85]  Christian Gieger,et al.  Combined analysis of genome-wide association studies for Crohn disease and psoriasis identifies seven shared susceptibility loci. , 2012, American journal of human genetics.

[86]  J. Arthur,et al.  Signaling downstream of p38 in psoriasis. , 2006, The Journal of investigative dermatology.

[87]  Ying Wang,et al.  Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus , 2009, Nature Genetics.

[88]  N. Van Rooijen,et al.  Activated macrophages are essential in a murine model for T cell-mediated chronic psoriasiform skin inflammation. , 2006, The Journal of clinical investigation.

[89]  B. Diamond,et al.  Autoimmune diseases , 2000, Bone Marrow Transplantation.

[90]  Matti Pirinen,et al.  A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1 , 2010, Nature Genetics.

[91]  Renhua Wu,et al.  A large-scale screen for coding variants predisposing to psoriasis , 2013, Nature Genetics.

[92]  James T. Elder,et al.  Association analyses identify six new psoriasis susceptibility loci in the Chinese population , 2010, Nature Genetics.

[93]  Judy H. Cho,et al.  A Genome-Wide Association Study Identifies IL23R as an Inflammatory Bowel Disease Gene , 2006, Science.

[94]  Gonçalo Abecasis,et al.  Deletion of the late cornified envelope LCE3B and LCE3C genes as a susceptibility factor for psoriasis , 2009, Nature Genetics.

[95]  J. Gudjonsson,et al.  Immunopathogenic mechanisms in psoriasis , 2004, Clinical and experimental immunology.

[96]  Liangdan Sun,et al.  Association analyses identifying two common susceptibility loci shared by psoriasis and systemic lupus erythematosus in the Chinese Han population , 2013, Journal of Medical Genetics.

[97]  M. Amagai,et al.  Adhesion of epidermal Langerhans cells to keratinocytes mediated by E-cadherin , 1993, Nature.

[98]  Andrew Blauvelt,et al.  Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo: implications for psoriasis pathogenesis. , 2009, The Journal of investigative dermatology.

[99]  R. B. Kjellerup,et al.  STAT1 expression and activation is increased in lesional psoriatic skin , 2013, The British journal of dermatology.

[100]  V. Kuchroo,et al.  TH-17 cells in the circle of immunity and autoimmunity , 2007, Nature Immunology.

[101]  A. Gaspari.  Innate and adaptive immunity and the pathophysiology of psoriasis. , 2006, Journal of the American Academy of Dermatology.

[102]  J. Krueger.  The immunologic basis for the treatment of psoriasis with new biologic agents. , 2002, Journal of the American Academy of Dermatology.

[103]  Frank O. Nestle,et al.  Mechanisms of Disease: Psoriasis. , 2009 .

[104]  M. Dhodapkar,et al.  Increased Expression of Interleukin 23 p19 and p40 in Lesional Skin of Patients with Psoriasis Vulgaris , 2004, The Journal of experimental medicine.

[105]  F. Nestle,et al.  Harnessing dendritic cells in inflammatory skin diseases , 2011, Seminars in immunology.

[106]  P. Helliwell,et al.  The prevalence of psoriatic arthritis in people with psoriasis. , 2009, Arthritis and rheumatism.

[107]  Francis S Collins,et al.  A HapMap harvest of insights into the genetics of common disease. , 2008, The Journal of clinical investigation.

[108]  Robert M. Plenge,et al.  Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis , 2011, Nature Genetics.

[109]  A. Menssen,et al.  Dominant lesional T cell receptor rearrangements persist in relapsing psoriasis but are absent from nonlesional skin: evidence for a stable antigen-specific pathogenic T cell response in psoriasis vulgaris. , 2001, The Journal of investigative dermatology.