Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Exacerbated inflammatory arthritis in response to hyperactive gp130 signalling is independent of IL-17A

Jones, Gareth Wyn, Greenhill, C. J., Williams, J. O., Nowell, Mari Ann, Williams, Anwen Sian ORCID: https://orcid.org/0000-0001-6118-020X, Jenkins, B. J. and Jones, S. A. 2013. Exacerbated inflammatory arthritis in response to hyperactive gp130 signalling is independent of IL-17A. Annals of the Rheumatic Diseases 72 (10) , pp. 1738-1742. 10.1136/annrheumdis-2013-203771

[thumbnail of Ann Rheum Dis-2013-Jones-1738-42.pdf]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (4MB) | Preview

Abstract

Objective Interleukin (IL)-17A producing CD4 T-cells (TH-17 cells) are implicated in rheumatoid arthritis (RA). IL-6/STAT3 signalling drives TH-17 cell differentiation, and hyperactive gp130/STAT3 signalling in the gp130F/F mouse promotes exacerbated pathology. Conversely, STAT1-activating cytokines (eg, IL-27, IFN-γ) inhibit TH-17 commitment. Here, we evaluate the impact of STAT1 ablation on TH-17 cells during experimental arthritis and relate this to IL-17A-associated pathology. Methods Antigen-induced arthritis (AIA) was established in wild type (WT), gp130F/F mice displaying hyperactive gp130-mediated STAT signalling and the compound mutants gp130F/F:Stat1−/− and gp130F/F: Il17a−/− mice. Joint pathology and associated peripheral TH-17 responses were compared. Results Augmented gp130/STAT3 signalling enhanced TH-17 commitment in vitro and exacerbated joint pathology. Ablation of STAT1 in gp130F/F mice (gp130F/F: Stat1−/− ) promoted the hyperexpansion of TH-17 cells in vitro and in vivo during AIA. Despite this heightened peripheral TH-17 cell response, disease severity and the number of joint-infiltrating T-cells were comparable with that of WT mice. Thus, gp130-mediated STAT1 activity within the inflamed synovium controls T-cell trafficking and retention. To determine the contribution of IL-17A, we generated gp130F/F:IL-17a−/− mice. Here, loss of IL-17A had no impact on arthritis severity. Conclusions Exacerbated gp130/STAT-driven disease in AIA is associated with an increase in joint infiltrating T-cells but synovial pathology is IL-17A independent.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: BMJ Publishing Group
ISSN: 0003-4967
Date of First Compliant Deposit: 30 March 2016
Last Modified: 04 May 2023 09:55
URI: https://orca.cardiff.ac.uk/id/eprint/85516

Citation Data

Cited 17 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics