Akademik Veri Yönetim Sistemi
5th International Molecular Immunology & Immunogenetics Congress, İzmir, Türkiye, 20 - 22 Ekim 2022, ss.89-90
Introduction: Multiple sclerosis (MS), which is one of the chronic autoimmune neurodegenerative diseases, is the most common cause of disability in young adults all over the world.As with a variety of autoimmune disorders, there is evidence of an altered level of tryptophan catabolism in MS patients. Indolamine-2,3-dioxygenase (IDO), the enzyme that initiates the breakdown of tryptophan, plays an important role in MS. On the other hand, activation of T lymphocytes requires recognition of the peptide-major histocompatibility complex and co-stimulatory signals provided by antigen-presenting cells. T cell activation without co-stimulus can lead to anergy. Method: In the first strategy, DCs were modified with lentiviral vector encoding only expression of IDO, which catabolizes tryptophan. In the second approach, DCs with a lentiviral vector encoding a fusion protein called CTLA4-KDEL that inhibits the expression of B7 (CD80/86) molecules on the cell surface by keeping co-stimulatory molecules in the endoplasmic reticulum. In the third approach, DCs with a lentiviral vector encoding IDO overexpression and silencing with shRNA CD80/CD86 in the same vector construct. Genetically modified DCs were administered intravenously to EAE model mice. Treated EAE model mice were followed for two weeks. Finally, histopathological examination was performed to evalute the lesions in the central nervous system. In addition, the brain and cerebellum were analyzed histochemically in order to observe demyelination that may cause damage to the protective covering (myelin sheath) that surrounds nerve fibers in brain. RESULTS We showed that downregulation of CD80 and CD86 expression alone or in DCs overexpressing IDO resulted in reduced clinical scores with these treatment strategies. However, the most effective treatment approach is the use of genetically modified overexpressed IDO and downregulated (CD80/CD86) in the same construct. Tolerance-inducing dendritic cells have exciting potential for the treatment of MS and other autoimmune diseases.
This study is being supported by TUBITAK(118S474)