Production of a lentiviral vector expressing vasoactive intestinal peptide for the transduction of dendritic cells: A potential therapy for autoimmune and inflammatory diseases

Inflammation is involved in the normal destruction of foreign pathogens, but a healthy immune system must balance its destructive capability with the ability to recognize self.  Autoimmune diseases such as multiple sclerosis, Crohn’s disease and type I diabetes are thought to result from a failure to discern self antigens from foreign antigens.  Currently, autoimmune and inflammatory diseases are treated with repeated systemic administrations of immunosuppressive drugs which have pleiotropic effects on the body and often lead to general immunosuppression.  Recent progress in biotechnologies provides tools such as viral vectors for cell-specific drug delivery.  Vasoactive intestinal peptide (VIP) is a promising therapeutic neuropeptide for treatment of autoimmune diseases because it inhibits both innate and adaptive immune responses and induces production of regulatory T cells.  Dendritic cells (DC) migrate throughout the periphery searching for invading pathogens and infected cells, passing information between the innate and adaptive immune systems.  Therefore, DC are potential vehicles for VIP gene-cell therapy.  It has previously been shown that lentiVIP-transduced DC are tolerogenic DC which might induce production of regulatory T cells, thereby reducing the immune response in autoimmunity.  Successful production of the lentiviral vector expressing VIP is crucial for future studies. My project will optimize the methods and efficiently produce lentiviral vectors expressing VIP for the successful transduction of DC.