Agonistic CD200R1 DNA Aptamers Are Potent Immunosuppressants That Prolong Allogeneic Skin Graft Survival

Molecular Therapy: Nucleic Acids

Aws Abdul-Wahid¹  Jean Gariépy¹  Marzena Cydzik¹  Aaron Prodeus¹  Eric Huang²  Reginald Gorczynski³  Ismat Khatri⁴ 

[1] Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada;Department of Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada;Departments of Surgery and Immunology, University Health Network, Toronto, Ontario, Canada;Transplant Research Division, Toronto Hospital and University Health Network, Toronto, Ontario, Canada;

关键词: aptamer;    CD200R1;    immunomodulation;    immunosuppression;    transplantation;   

DOI  :  10.1038/mtna.2014.41

来源: DOAJ

【 摘 要 】

CD200R1 expressed on the surface of myeloid and lymphoid cells delivers immune inhibitory signals to modulate inflammation when engaged with its ligand CD200. Signalling through CD200/CD200R1 has been implicated in a number of immune-related diseases including allergy, infection, cancer and transplantation, as well as several autoimmune disorders including arthritis, systemic lupus erythematosus, and multiple sclerosis. We report the development and characterization of DNA aptamers, which bind to murine CD200R1 and act as potent signalling molecules in the absence of exogenous CD200. These agonistic aptamers suppress cytotoxic T-lymphocyte induction in 5-day allogeneic mixed leukocyte culture and induce rapid phosphorylation of the CD200R1 cytoplasmic tail thereby initiating immune inhibitory signalling. PEGylated conjugates of these aptamers show significant in vivo immunosuppression and enhance survival of allogeneic skin grafts as effectively as soluble CD200Fc. As DNA aptamers exhibit inherent advantages over conventional protein-based therapeutics including low immunogenicity, ease of synthesis, low cost, and long shelf life, such CD200R1 agonistic aptamers may emerge as useful and safe nonsteroidal anti-inflammatory therapeutic agents.

【 授权许可】

Unknown