title: The immunogenetics of Psoriasis: A comprehensive review.
abstract: Psoriasis vulgaris is a common, chronic inflammatory skin disease with a complex etiology involving genetic risk factors and environmental triggers. Here we describe the many known genetic predispositions of psoriasis with respect to immune genes and their encoded pathways in psoriasis susceptibility. These genes span an array of functions that involve antigen presentation (HLA-Cw6, ERAP1, ERAP2, MICA), the IL-23 axis (IL12Bp40, IL23Ap19, IL23R, JAK2, TYK2), T-cell development and T-cells polarization (RUNX1, RUNX3, STAT3, TAGAP, IL4, IL13), innate immunity (CARD14, c-REL, TRAF3IP2, DDX58, IFIH1), and negative regulators of immune responses (TNIP1, TNFAIP3, NFKBIA, ZC3H12C, IL36RN, SOCS1). The contribution of some of these gene products to psoriatic disease has also been revealed in recent years through targeting of key immune components, such as the Th17/IL-23 axis which has been highly successful in disease treatment. However, many of the genetic findings involve immune genes with less clear roles in psoriasis pathogenesis. This is particularly the case for those genes involved in innate immunity and negative regulation of immune specific pathways. It is possible that risk alleles of these genes decrease the threshold for the initial activation of the innate immune response. This could then lead to the onslaught of the pathogenic adaptive immune response known to be active in psoriatic skin. However, precisely how these various genes affect immunobiology need to be determined and some are speculated upon in this review. These novel genetic findings also open opportunities to explore novel therapeutic targets and potentially the development of personalized medicine, as well as discover new biology of human skin disease.
authors.affiliation: The Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY 10065, USA; Dermira, Inc. Menlo Park, CA 94025, USA.
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Harden
authors.affiliation: The Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: James G
authors.initials: JG
authors.lastname: Krueger
authors.affiliation: National Heart and Lung Institute, Imperial College, London SW3 6LY, UK. Electronic address: A.bowcock@imperial.ac.uk.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Bowcock
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate; D007125:Immunogenetics; D056747:Immunomodulation; D011565:Psoriasis / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
keywords: Genetics; Immunology; Innate immunity; Negative regulators; Psoriasis; Th17-axis