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

Research output: Contribution to journalArticle

27 Citations (Scopus)

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

Fingerprint

Gene transfer
Psoriatic Arthritis
Interleukin-17
Hyperplasia
Bone
Bone and Bones
Genes
Pathology
Osteoclasts
Bone Resorption
Skin
Joints
Parakeratosis
Cytokines
Inflammation
Experimental Arthritis
Biomarkers
Skin Diseases
Arthritis
Animals

ASJC Scopus subject areas

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

Cite this

IL-17A gene transfer induces bone loss and epidermal hyperplasia associated with psoriatic arthritis. / Adamopoulos, Iannis; Suzuki, Erika; Chao, Cheng Chi; Gorman, Dan; Adda, Sarvesh; Maverakis, Emanual Michael; Zarbalis, Konstantinos; Geissler, Richard; Asio, Agelio; Blumenschein, Wendy M.; Mcclanahan, Terrill; De Malefyt, Rene Waal; Gershwin, M. Eric; Bowman, Edward P.

In: Annals of the Rheumatic Diseases, Vol. 74, No. 6, 01.06.2015, p. 1284-1292.

Research output: Contribution to journalArticle

Adamopoulos, I, Suzuki, E, Chao, CC, Gorman, D, Adda, S, Maverakis, EM, Zarbalis, K, Geissler, R, Asio, A, Blumenschein, WM, Mcclanahan, T, De Malefyt, RW, Gershwin, ME & Bowman, EP 2015, 'IL-17A gene transfer induces bone loss and epidermal hyperplasia associated with psoriatic arthritis', Annals of the Rheumatic Diseases, vol. 74, no. 6, pp. 1284-1292. https://doi.org/10.1136/annrheumdis-2013-204782
Adamopoulos, Iannis ; Suzuki, Erika ; Chao, Cheng Chi ; Gorman, Dan ; Adda, Sarvesh ; Maverakis, Emanual Michael ; Zarbalis, Konstantinos ; Geissler, Richard ; Asio, Agelio ; Blumenschein, Wendy M. ; Mcclanahan, Terrill ; De Malefyt, Rene Waal ; Gershwin, M. Eric ; Bowman, Edward P. / IL-17A gene transfer induces bone loss and epidermal hyperplasia associated with psoriatic arthritis. In: Annals of the Rheumatic Diseases. 2015 ; Vol. 74, No. 6. pp. 1284-1292.
@article{fae0a4924bdd4f978ff7a56268e78db6,
title = "IL-17A gene transfer induces bone loss and epidermal hyperplasia associated with psoriatic arthritis",
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+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.",
author = "Iannis Adamopoulos and Erika Suzuki and Chao, {Cheng Chi} and Dan Gorman and Sarvesh Adda and Maverakis, {Emanual Michael} and Konstantinos Zarbalis and Richard Geissler and Agelio Asio and Blumenschein, {Wendy M.} and Terrill Mcclanahan and {De Malefyt}, {Rene Waal} and Gershwin, {M. Eric} and Bowman, {Edward P.}",
year = "2015",
month = "6",
day = "1",
doi = "10.1136/annrheumdis-2013-204782",
language = "English (US)",
volume = "74",
pages = "1284--1292",
journal = "Annals of the Rheumatic Diseases",
issn = "0003-4967",
publisher = "BMJ Publishing Group",
number = "6",

}

TY - JOUR

T1 - IL-17A gene transfer induces bone loss and epidermal hyperplasia associated with psoriatic arthritis

AU - Adamopoulos, Iannis

AU - Suzuki, Erika

AU - Chao, Cheng Chi

AU - Gorman, Dan

AU - Adda, Sarvesh

AU - Maverakis, Emanual Michael

AU - Zarbalis, Konstantinos

AU - Geissler, Richard

AU - Asio, Agelio

AU - Blumenschein, Wendy M.

AU - Mcclanahan, Terrill

AU - De Malefyt, Rene Waal

AU - Gershwin, M. Eric

AU - Bowman, Edward P.

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.

UR - http://www.scopus.com/inward/record.url?scp=84934978126&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84934978126&partnerID=8YFLogxK

U2 - 10.1136/annrheumdis-2013-204782

DO - 10.1136/annrheumdis-2013-204782

M3 - Article

VL - 74

SP - 1284

EP - 1292

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - 6

ER -