In:
Annals of the Rheumatic Diseases, BMJ, Vol. 74, No. 6 ( 2015-06), p. 1284-1292
Abstract:
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 + Gr1 low 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 + Gr1 high 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.
Type of Medium:
Online Resource
ISSN:
0003-4967
,
1468-2060
DOI:
10.1136/annrheumdis-2013-204782
Language:
English
Publisher:
BMJ
Publication Date:
2015
detail.hit.zdb_id:
1481557-6
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