Treatment of murine lupus with PD-LIg.
The binding of programmed death 1 (PD-1) to its ligands PD-L1 and PD-L2 on antigen-presenting cells has been proven to turn off autoreactive T cells and induce peripheral tolerance. In this study, fusion proteins linking the extracellular domains of murine PD-1, PD-L1 and PD-L2 to the Fc portion of a mouse immunoglobulin G2a monoclonal antibody were generated and characterized. Onset of proteinuria was delayed with mice treated with PD-LIg fusion proteins, while serum concentrations of anti-dsDNA and anti-histone antibodies were reduced by the treatment of PD-LIg without decreasing total IgG with significantly improved survival. Importantly, PD-L1Ig treatment was the most efficacious in delaying the onset of proteinuria, blocking auto-antibody production, and prolonging life time, including a delayed treatment until disease progression. These findings indicate that human PD-L1Ig fusion proteins may play an important role in conquering humans' autoimmune diseases.
Department of Pathophysiology, Key Lab for Shock and Microcirculation Research of Guangdong, Southern Medical University, Guangzhou 510515, PR China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou 510630, PR China; Central Laboratory, Navy General Hospital, 6 Fucheng Road, Beijing 100048, PR China.
Hui
H
Zhou
Central Laboratory, Navy General Hospital, 6 Fucheng Road, Beijing 100048, PR China.
Lijuan
L
Xiong
Central Laboratory, Navy General Hospital, 6 Fucheng Road, Beijing 100048, PR China.
Yuxiao
Y
Wang
The Third School of Clinical Medicine, Southern Medical University, Guangzhou 510630, PR China; Central Laboratory, Navy General Hospital, 6 Fucheng Road, Beijing 100048, PR China.
Li
L
Ding
Department of Biophysics, College of Basic Medical Sciences, Second Military Medical University, Shanghai 200433, PR China.
Shi
S
Hu
Department of Pathophysiology, Key Lab for Shock and Microcirculation Research of Guangdong, Southern Medical University, Guangzhou 510515, PR China. Electronic address: 15602239057@163.com.
Ming
M
Zhao
The Third School of Clinical Medicine, Southern Medical University, Guangzhou 510630, PR China; Central Laboratory, Navy General Hospital, 6 Fucheng Road, Beijing 100048, PR China. Electronic address: hzzhoulj@126.com.
Lijun
L
Zhou
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000503:physiopathology; D051379:Mice; D016513:Mice, SCID; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000627:therapeutic use*
D007074:Immunoglobulin G; D061027:Programmed Cell Death 1 Ligand 2 Protein
Murine lupus; PD-1; PD-L; Targeted therapy