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Arthritis Res Ther. 2015 Nov 25;17:340. doi: 10.1186/s13075-015-0859-z.

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

Author information

1
Jiangsu Institute of Clinical Immunology, First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
2
Jiangsu Province Key Laboratory of Stem Cell Research, Soochow University, Suzhou, 215006, China.
3
Department of Rheumatology, Third Affiliated Hospital of Soochow University, Changzhou, 213003, China.
4
Jiangsu Institute of Clinical Immunology, First Affiliated Hospital of Soochow University, Suzhou, 215006, China. xueguangzh@126.com.
5
Jiangsu Province Key Laboratory of Stem Cell Research, Soochow University, Suzhou, 215006, China. xueguangzh@126.com.

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.

PMID:
26608464
PMCID:
PMC4659197
DOI:
10.1186/s13075-015-0859-z
[Indexed for MEDLINE]
Free PMC Article

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