Elsevier

Immunology Letters

Volume 227, November 2020, Pages 96-101
Immunology Letters

Abnormal membrane-bound and soluble programmed death ligand 2 (PD-L2) expression in systemic lupus erythematosus is associated with disease activity

https://doi.org/10.1016/j.imlet.2020.09.001Get rights and content

Highlights

  • •

    Enhanced mPD-L2 expression and reduced sPD-L2 levels in SLE patients” and “PD-L2 may be a promising biomarker and associated with the pathogenesis of SLE.

Abstract

Programmed death ligand (PD-L) 2 and PD-L1 are the second and first ligands, respectively, for programmed cell death-1 protein (PD-1), which is one of the key factors responsible for inhibitory T cell signaling, mediating mechanisms of tolerance and providing immune homeostasis. Studies have shown that PD-1 and its ligand PD-L1 are abnormally expressed in autoimmune diseases, such as rheumatoid arthritis and autoimmune hepatitis, but its other ligand, PD-L2, has rarely been studied. This study analyzed the changes in membrane-bound PD-L2 expression in peripheral blood mononuclear cells and soluble PD-L2 (sPD-L2) levels in the serum of patients with systemic lupus erythematosus (SLE) to explore the relationship between PD-L2 expression with disease activity and related test parameters. Our results showed that membrane-bound PD-L2 expression on monocytes was significantly higher and the sPD-L2 levels were significantly lower in SLE patients than in healthy subjects. Patients with active SLE accompanied by lupus nephritis, joint pain, and clinical manifestations of oral ulcers had relatively low secretion of sPD-L2. In addition, this secretion level was significantly and positively correlated with complement components 3 and 4 (C3/C4). These results suggest that PD-L2 may be a promising biomarker associated with the pathogenesis of SLE.

Section snippets

INTRODUCTION

Programmed death ligand (PD-L) 2 is a member of the B7 family of membrane proteins and a ligand of the costimulatory molecule programmed cell death-1 protein (PD-1). It was first identified in 2001 when studying the function of PD-L1 [1]. PD-1 and its ligands, PD-L1 and PD-L2, are important immunomodulatory molecules and play a role in the pathogenesis of autoimmune diseases [[2], [3], [4], [5]]. They are instrumental in maintaining immune tolerance, and blocking this pathway can exacerbate

Research subjects

Peripheral blood samples were obtained from 78 SLE patients seen between October 2014 and July 2015 in the Department of Rheumatology of Suzhou Hospital of Traditional Chinese Medicine, Jiangsu Province, China. Patients fulfilled 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria for SLE and patients with comorbidities of cancers or infections were excluded [12]. All patients had not received any hormone or immunotherapy within half a year of sample collection. The disease

Membrane-bound PD-L2 is increased in SLE PBMCs

Studies have shown that PD-L2 is not expressed on the surface of resting lymphocytes but is expressed on activated monocytes [9,13]. Confirming this, FACS analysis of PBMCs from SLE patients found PD-L2 expression (12.51% expression rate) was significantly higher compared to expression levels in control cells (6.76% expression rate) (p < 0.05, Fig. 1).

sPD-L2 is decreased in blood from individuals with SLE

sPD-L2 levels in blood from SLE patients (2744 ± 119 pg/mL) were significantly lower than levels in control individual samples (4857 ± 102.6

DISCUSSION

Immune checkpoint (IC) molecules are a group of protein they can attenuate T cell responses to prevent autoimmunity and maintain immune homeostasis. IC inhibitors (ICs) therapy has emerged as an important new approach to treat malignancy. The clinical success of anti-CTLA4 [14,15] and anti-PD1 blocking antibody (Ab) [16,17] in various cancers encourages more active research and drug development effort. However, in the processing of ICI treatment there are reports about drugs blocking PD-1/PD-L

Author contributions

Research was designed by Jing sun. Patient samples and data were provided by Xiaohui Fang. Cell proliferation, migration and tube formation was performed by Min Tong and Jie Yang. Cytokine analysis was performed by Yundi Guo. The manuscript was critically reviewed by all authors. The study was supervised by Jing Sun.

Ab: antibody

C3: components 3

C4:components 4

CRP: C-reactive protein

ESR: erythrocyte sedimentation rate

FITC: fluorescein isothiocyanate

IC: Immune checkpoint

ICs:IC inhibitors

Ig:

Declaration of Competing Interest

The authors report no declarations of interest.

Acknowledgments

This work was supported by grants from the Jiangsu Engineering Research Center (Medical Diagnostic Antibody), and Jiangsu Provincial Medical Talent (Sun Jing).The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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