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IL-17 receptor and its functional significance in psoriatic arthritis

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Abstract

To delineate the functional significance of IL-17 Receptor (IL-17RA) and characterize the IL-17 producing T cell (Th17) subpopulation in psoriatic arthritis (PsA). Mononuclear cells from blood and synovial fluid (SF) were obtained from PsA (n = 20), rheumatoid arthritis (RA, n = 20) and osteoarthritis (OA, n = 20) patients. Synoviocytes (FLS) were isolated from the synovium of RA (n = 5), PsA (n = 5) and OA (n = 5) patients. IL-17RA expression in FLS was identified by western blotting (WB) and flowcytometry. T lymphocytes derived from the SF of these patients were studied to identify and phenotype the Th17 cells. The functional significance of IL-17RA was determined by evaluating its regulatory role on the production of proinflammatory cytokines and endopeptidase. IL-17RA expression was found to be significantly higher in FLS of RA (15.7% ± 4.9) and PsA (4.5% ± 0.9) in comparison to OA (1.14% ± 0.9). Western blot analyses showed that the relative intensity (RI) of IL-17RA protein was higher in RA and PsA compared to OA (Fisher exact, P < 0.01). A significant enrichment of IL-17-producing CD4+ T cells (7.9% ± 2.8) was observed in the SF of PsA patients compared to that of OA patients (P < .001). Compared to OA-FLS, recombinant IL-17 induced higher levels of IL-6, IL-8, and MMP-3 production in PsA-FLS. Blockage of IL-17RA with an anti-IL-17RA antibody inhibited the production of IL-6, IL-8, and MMP-3. This is the first report to demonstrate the functional significance of IL-17RA in PsA. Results of this study support the hypothesis that IL-17RA blocking antibodies have the potential to be a therapeutic option for psoriatic arthritis.

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Abbreviations

IL-17:

Interleukin 17

IL-17R:

IL-17 receptor

Th17:

IL-17 producing T helper cells

IFN-γ:

Interferon-γ

FLS:

Fibroblast like synovial cells

MMP-3:

Matrix metalloproteinase-3

OA:

Osteoarthritis

PBMC:

Peripheral blood mononuclear cells

PsA:

Psoriatic arthritis

RORγt:

Retinoic acid–related orphan receptor γt

SFMC:

Synovial fluid derived mononuclear cells

TGFβ:

Transforming growth factor beta

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Acknowledgment

This study was supported by a grant from East Bay Institute for Research and Education, Martinez, CA.

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Authors and Affiliations

  1. Division of Rheumatology, Allergy & Clinical Immunology, University of California Davis School of Medicine & VA Medical Center Sacramento, 1911 Geneva Place, Davis, CA, 95618, USA

    Siba P. Raychaudhuri & Smriti K. Raychaudhuri

  2. Stanford University School of Medicine, Immunology & Rheumatology, Stanford, CA, USA

    Mark C. Genovese

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  1. Siba P. Raychaudhuri
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Correspondence to Siba P. Raychaudhuri.

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Raychaudhuri, S.P., Raychaudhuri, S.K. & Genovese, M.C. IL-17 receptor and its functional significance in psoriatic arthritis. Mol Cell Biochem 359, 419–429 (2012). https://doi.org/10.1007/s11010-011-1036-6

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