IL-17A gene transfer induces bone loss and epidermal hyperplasia associated with psoriatic arthritis

Iannis Adamopoulos, Erika Suzuki, Cheng Chi Chao, Dan Gorman, Sarvesh Adda, Emanual Michael Maverakis, Konstantinos Zarbalis, Richard Geissler, Agelio Asio, Wendy M. Blumenschein, Terrill Mcclanahan, Rene Waal De Malefyt, M. Eric Gershwin, Edward P. Bowman

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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. 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<sup>+</sup>CD11b<sup>+</sup>Gr1<sup>low</sup> 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<sup>+</sup>Gr1<sup>high</sup> 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.

Original languageEnglish (US)
Pages (from-to)1284-1292
Number of pages9
JournalAnnals of the Rheumatic Diseases
Volume74
Issue number6
DOIs
StatePublished - Jun 1 2015

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ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Allergy

Cite this

Adamopoulos, I., Suzuki, E., Chao, C. C., Gorman, D., Adda, S., Maverakis, E. M., Zarbalis, K., Geissler, R., Asio, A., Blumenschein, W. M., Mcclanahan, T., De Malefyt, R. W., Gershwin, M. E., & Bowman, E. P. (2015). IL-17A gene transfer induces bone loss and epidermal hyperplasia associated with psoriatic arthritis. Annals of the Rheumatic Diseases, 74(6), 1284-1292. https://doi.org/10.1136/annrheumdis-2013-204782