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