NDLI: Exacerbated in fl ammatory arthritis in response to hyperactive gp 130 signalling is independent of IL-17 A

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Exacerbated in fl ammatory arthritis in response to hyperactive gp 130 signalling is independent of IL-17 A

Content Provider	Semantic Scholar
Author	Jones, Gareth W. Greenhill, Claire J. Williams, Jessica O. Nowell, Mari Ann Williams, Anwen Siân Jenkins, Brendan J. Jones, Sarah A.
Copyright Year	2013
Abstract	To cite: Jones GW, Greenhill CJ, Williams JO, et al. Ann Rheum Dis Published Online First: [please include Day Month Year] doi:10.1136/ annrheumdis-2013-203771 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 gp130 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), gp130 mice displaying hyperactive gp130-mediated STAT signalling and the compound mutants gp130:Stat1 and gp130: 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 gp130 mice (gp130: 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 gp130: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.
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://ard.bmj.com/content/annrheumdis/early/2013/07/26/annrheumdis-2013-203771.full.pdf
Alternate Webpage(s)	http://ard.bmj.com/content/annrheumdis/72/10/1738.full.pdf
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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