RT Journal Article
SR Electronic
T1 IL-17A gene transfer induces bone loss and epidermal hyperplasia associated with psoriatic arthritis
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 1284
OP 1292
DO 10.1136/annrheumdis-2013-204782
VO 74
IS 6
A1 Iannis E Adamopoulos
A1 Erika Suzuki
A1 Cheng-Chi Chao
A1 Dan Gorman
A1 Sarvesh Adda
A1 Emanual Maverakis
A1 Konstantinos Zarbalis
A1 Richard Geissler
A1 Agelio Asio
A1 Wendy M Blumenschein
A1 Terrill Mcclanahan
A1 Rene De Waal Malefyt
A1 M Eric Gershwin
A1 Edward P Bowman
YR 2015
UL http://ard.bmj.com/content/74/6/1284.abstract
AB 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.