TY - JOUR
T1 - IL-17A gene transfer induces bone loss and epidermal hyperplasia associated with psoriatic arthritis
AU - Adamopoulos, Iannis E.
AU - Suzuki, Erika
AU - Chao, Cheng Chi
AU - Gorman, Dan
AU - Adda, Sarvesh
AU - Maverakis, Emanual
AU - Zarbalis, Konstantinos
AU - Geissler, Richard
AU - Asio, Agelio
AU - Blumenschein, Wendy M.
AU - Mcclanahan, Terrill
AU - De Malefyt, Rene Waal
AU - Eric Gershwin, M.
AU - Bowman, Edward P.
N1 - Publisher Copyright:
© 2015, BMJ Publishing Group. All rights reserved.
PY - 2015/6/1
Y1 - 2015/6/1
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.
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.
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U2 - 10.1136/annrheumdis-2013-204782
DO - 10.1136/annrheumdis-2013-204782
M3 - Article
C2 - 24567524
AN - SCOPUS:84934978126
SN - 0003-4967
VL - 74
SP - 1284
EP - 1292
JO - Annals of the rheumatic diseases
JF - Annals of the rheumatic diseases
IS - 6
ER -