TY - JOUR 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 SP - 1284 LP - 1292 DO - 10.1136/annrheumdis-2013-204782 VL - 74 IS - 6 AU - Iannis E Adamopoulos AU - Erika Suzuki AU - Cheng-Chi Chao AU - Dan Gorman AU - Sarvesh Adda AU - Emanual Maverakis AU - Konstantinos Zarbalis AU - Richard Geissler AU - Agelio Asio AU - Wendy M Blumenschein AU - Terrill Mcclanahan AU - Rene De Waal Malefyt AU - M Eric Gershwin AU - Edward P Bowman Y1 - 2015/06/01 UR - http://ard.bmj.com/content/74/6/1284.abstract N2 - 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. ER -