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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2015

Open Access 01-12-2015 | Research article

Soluble PD-1 aggravates progression of collagen-induced arthritis through Th1 and Th17 pathways

Authors: Cuiping Liu, Juean Jiang, Li Gao, Xiaoting Wang, Xiaohan Hu, Min Wu, Jian Wu, Ting Xu, Qin Shi, Xueguang Zhang

Published in: Arthritis Research & Therapy | Issue 1/2015

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Abstract

Introduction

The programmed cell death 1 (PD-1) protein is a critical regulator of T-cell activation and is also an important therapeutic target for autoimmune diseases. Little is known about the regulation and functional properties of the soluble PD-1 (sPD-1) variant. The aim of this study was to examine the role of sPD-1 in the regulation of human and murine rheumatoid arthritis (RA).

Methods

Expression of cytokines and sPD-1 in sera, synovial fluid, and peripheral blood (PB) mononuclear cells of patients with RA were analyzed by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. PD-1 function was assessed in PB T cells after stimulation of the cells with anti-CD3 and PD-L1-Fc to crosslink PD-1. Recombinant PD-1-Fc was injected intraperitoneally into DBA/1 mice with collagen-induced arthritis (CIA) to analyze the function of sPD-1 in vivo.

Results

High concentrations of sPD-1 were found in sera and synovial fluid of patients with RA. The levels of serum sPD-1 were significantly correlated with titers of rheumatoid factor (RF) (r = 0.306, p = 0.005) and 28-joint Disease Activity Score (r = 0.545, p < 0.001). Further characterization of sPD-1 revealed that it functionally blocked the inhibitory effect of membrane-bound PD-1 on T-cell activation. Interferon γ, tumor necrosis factor α, and interleukin 17A were identified as inducers of sPD-1 in vitro. Moreover, PD-1-Fc enhanced proinflammatory cytokine expression, generation of Th1 cells and Th17 cells, and joint pathology in a CIA model.

Conclusions

sPD-1 regulates peripheral T-cell responses in both human and murine RA. Thus, sPD-1 may represent an additional biomarker or target in immunomodulatory therapy for RA.
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Metadata
Title
Soluble PD-1 aggravates progression of collagen-induced arthritis through Th1 and Th17 pathways
Authors
Cuiping Liu
Juean Jiang
Li Gao
Xiaoting Wang
Xiaohan Hu
Min Wu
Jian Wu
Ting Xu
Qin Shi
Xueguang Zhang
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2015
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-015-0859-z

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