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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 6/2009

Open Access 01-12-2009 | Research article

Interleukin-23 is critical for full-blown expression of a non-autoimmune destructive arthritis and regulates interleukin-17A and RORγt in γδ T cells

Authors: Ferry Cornelissen, Adriana MC Mus, Patrick S Asmawidjaja, Jan Piet van Hamburg, Joel Tocker, Erik Lubberts

Published in: Arthritis Research & Therapy | Issue 6/2009

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Abstract

Introduction

Interleukin (IL)-23 is essential for the development of various experimental autoimmune models. However, the role of IL-23 in non-autoimmune experimental arthritis remains unclear. Here, we examined the role of IL-23 in the non-autoimmune antigen-induced arthritis (AIA) model. In addition, the regulatory potential of IL-23 in IL-17A and retinoic acid-related orphan receptor gamma t (RORγt) expression in CD4+ and TCRγδ+ T cells was evaluated systemically as well as at the site of inflammation.

Methods

Antigen-induced arthritis was induced in wild-type, IL-23p19-deficient and IL-17 Receptor A - knockout mice. At different time points, synovial cytokine and chemokine expression was measured. At days 1 and 7 of AIA, splenocytes and joint-infiltrating cells were isolated and analyzed for intracellular IL-17A and interferon (IFN)-γ ex-vivo by flow cytometry. In splenic CD4+ and TCRγδ+ T cells gene expression was quantified by flow cytometry and quantitative PCR.

Results

IL-23 was critical for full-blown AIA. Lack of IL-23 did not prevent the onset of joint inflammation but stopped the progression to a destructive synovitis. IL-23 regulated IL-17A expression in CD4+ T cells in the spleen. Of note, IL-17A and IFN-γ expression was reduced in CD4+ T cells in the inflamed joints of IL-23p19-deficient mice. Interestingly, IL-23 was also critical for the induction of IL-17A and RORγt but not IFN-γ in TCRγδ+ T cells in the inflamed joints. The importance of the IL-23/IL-17 axis was further confirmed using IL-17 Receptor A knockout mice showing significantly milder AIA compared to control mice, with a disease course comparable to that of IL-23p19-deficient mice.

Conclusions

These data show that IL-23 is critical for full-blown expression of a non-autoimmune destructive arthritis and regulates the proportion of IL-17A and IFN-γ-positive CD4+ T cells at the site of inflammation. Furthermore, IL-23 regulates IL-17A and RORγt expression in TCRγδ T cells in arthritis. These findings indicate that regulating the IL-23 pathway may have therapeutic potential in non-autoimmune arthritis.
Appendix
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Metadata
Title
Interleukin-23 is critical for full-blown expression of a non-autoimmune destructive arthritis and regulates interleukin-17A and RORγt in γδ T cells
Authors
Ferry Cornelissen
Adriana MC Mus
Patrick S Asmawidjaja
Jan Piet van Hamburg
Joel Tocker
Erik Lubberts
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 6/2009
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar2893

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