title: IL-17A gene transfer induces bone loss and epidermal hyperplasia associated with psoriatic arthritis.
abstract: BACKGROUND
  Psoriatic arthritis (PsA) is a chronic inflammatory disease characterised by clinical features that include bone loss and epidermal hyperplasia. Aberrant cytokine expression has been linked to joint and skin pathology; however, it is unclear which cytokines are critical for disease initiation. Interleukin 17A (IL-17A) participates in many pathological immune responses; however, its role in PsA has not been fully elucidated.
  
  
  OBJECTIVE
  To determine the role of IL-17A in epidermal hyperplasia and bone destruction associated with psoriatic arthritis.
  
  
  METHODS
  An in vivo gene transfer approach was used to investigate the role of IL-17A in animal models of inflammatory (collagen-induced arthritis) and non-inflammatory (receptor activator of NF-κB ligand (RANKL)-gene transfer) bone loss.
  
  
  RESULTS
  IL-17A gene transfer induced the expansion of IL-17RA(+)CD11b(+)Gr1(low) osteoclast precursors and a concomitant elevation of biomarkers indicative of bone resorption. This occurred at a time preceding noticeable joint inflammation, suggesting that IL-17A is critical for the induction of pathological bone resorption through direct activation of osteoclast precursors. Moreover, IL-17A induced a second myeloid population CD11b(+)Gr1(high) neutrophil-like cells, which was associated with cutaneous pathology including epidermal hyperplasia, parakeratosis and Munro's microabscesses formation.
  
  
  CONCLUSIONS
  Collectively, these data support that IL-17A can play a key role in the pathogenesis of inflammation-associated arthritis and/or skin disease, as observed in PsA.
authors.affiliation: Discovery Research, Merck Research Laboratories, Palo Alto, California, USA Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, USA Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California.
authors.forename: Iannis E
authors.initials: IE
authors.lastname: Adamopoulos
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, USA.
authors.forename: Erika
authors.initials: E
authors.lastname: Suzuki
authors.affiliation: Discovery Research, Merck Research Laboratories, Palo Alto, California, USA.
authors.forename: Cheng-Chi
authors.initials: CC
authors.lastname: Chao
authors.affiliation: Discovery Research, Merck Research Laboratories, Palo Alto, California, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Gorman
authors.affiliation: Discovery Research, Merck Research Laboratories, Palo Alto, California, USA.
authors.forename: Sarvesh
authors.initials: S
authors.lastname: Adda
authors.affiliation: Department of Dermatology, University of California, Davis, USA.
authors.forename: Emanual
authors.initials: E
authors.lastname: Maverakis
authors.affiliation: Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California, Department of Pathology and Laboratory Medicine, University of California, Davis, USA.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Zarbalis
authors.affiliation: Anatomic Pathology & Clinical Laboratory Departments, Stanford University, Palo Alto, California, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Geissler
authors.affiliation: Discovery Research, Merck Research Laboratories, Palo Alto, California, USA.
authors.forename: Agelio
authors.initials: A
authors.lastname: Asio
authors.affiliation: Discovery Research, Merck Research Laboratories, Palo Alto, California, USA.
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Blumenschein
authors.affiliation: Discovery Research, Merck Research Laboratories, Palo Alto, California, USA.
authors.forename: Terrill
authors.initials: T
authors.lastname: Mcclanahan
authors.affiliation: Discovery Research, Merck Research Laboratories, Palo Alto, California, USA.
authors.forename: Rene
authors.initials: R
authors.lastname: De Waal Malefyt
authors.affiliation: Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, USA.
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
authors.affiliation: Discovery Research, Merck Research Laboratories, Palo Alto, California, USA.
authors.forename: Edward P
authors.initials: EP
authors.lastname: Bowman
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015535:Arthritis, Psoriatic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001862:Bone Resorption / Q000235:genetics*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004817:Epidermis / Q000378:metabolism / Q000473:pathology*; D018014:Gene Transfer Techniques; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology; D020381:Interleukin-17 / Q000235:genetics*; D051379:Mice; D010010:Osteoclasts / Q000378:metabolism*; D053245:RANK Ligand / Q000235:genetics
chemical_list: D016207:Cytokines; C098680:Il17a protein, mouse; D020381:Interleukin-17; D053245:RANK Ligand
keywords: Arthritis; Autoimmune Diseases; Psoriatic Arthritis