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IL-17A gene transfer induces bone loss and epidermal hyperplasia associated with psoriatic arthritis
  1. Iannis E Adamopoulos1,2,3,
  2. Erika Suzuki2,
  3. Cheng-Chi Chao1,
  4. Dan Gorman1,
  5. Sarvesh Adda1,
  6. Emanual Maverakis4,
  7. Konstantinos Zarbalis3,5,
  8. Richard Geissler6,
  9. Agelio Asio1,
  10. Wendy M Blumenschein1,
  11. Terrill Mcclanahan1,
  12. Rene De Waal Malefyt1,
  13. M Eric Gershwin2,
  14. Edward P Bowman1
  1. 1Discovery Research, Merck Research Laboratories, Palo Alto, California, USA
  2. 2Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, USA
  3. 3Institute for Pediatric Regenerative Medicine, Shriners Hospitals for Children Northern California,
  4. 4Department of Dermatology, University of California, Davis, USA
  5. 5Department of Pathology and Laboratory Medicine, University of California, Davis, USA
  6. 6Anatomic Pathology & Clinical Laboratory Departments, Stanford University, Palo Alto, California, USA
  1. Correspondence to Iannis E Adamopoulos, Shriners Hospital for Children Northern California, Institute for Pediatric Regenerative Medicine, 2425 Stockton Blvd, Room 653A, Sacramento, CA 95817, USA; iannis{at} and Edward P Bowman, Department of Therapeutic Area Biology and Pharmacology, Merck Research Laboratories, 901 California Avenue, Palo Alto, CA 94304, USA;


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.

Design 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+Gr1low 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+Gr1high 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.

  • Arthritis
  • Psoriatic Arthritis
  • Autoimmune Diseases

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