القای سلول‌های دندریتیک تولروژن موشی با تنظیم کاهشی ملکول کمک تحریکی CD40 با استفاده از وکتور لنتی ویروس

Induction of Tolerogenic Murine Dendritic Cells by Downregulating the Co-stimulatory Molecule of CD40 Using Lentivirus Vector Mahmoodzadeh A1, Pourfatollah AA1, Karimi MH2, Moazzeni SM1 1Dept. of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran 2Transplantation Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran. Correspond Author: Pourfatollah AA, Dept. of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran E-mail: [email protected] Received: 14 May 2014 Accepted: 13 Jul 2014 Background and Objective: The important role of co-stimulatory molecules in immunological responses has been clearly demonstrated. With the development of new methods in molecular immunology, preventing the co-stimulatory signals in order to induce tolerance has emerged as a novel strategy. RNA interference is a new method that can specifically and effectively reduce target gene expression. Materials and Methods: In this study, we used a lentiviral system to target the expression of CD40 gene in dendritic cells. ShRNA sequence is able to reduce the expression of CD40 gene on murine dendritic cells. Results: Our results indicate 64-fold decreased expression of CD40 mRNA in the group receiving lentiviral shRNACD40 as well as 31% decrease in expression of CD40 protein on the surface of dentridic cells (p<0.0001). Also, dendritic cells cannot stimulate T cells upon contact with them. Conclusion: This study indicates that a decrease in expression of CD40 molecule induces tolerogenic dendritic cells and prevents Th1 immunological response. Prevention of Th1 response would shift the immunological responses to Th2 response, and this type of response can be effective in autoimmune diseases including rheumatoid arthritis and type I diabetes. References 1- Groux H, Fournier N, Cottrez F. Role of dendritic cells in the generation of regulatory T cells. 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