Research Information System
6th International Molecular Immunology & Immunogenetics Congress (MIMIC-VI), İstanbul, Turkey, 27 - 30 April 2025, pp.17, (Summary Text)
approximately 1% of the population, leading to progressive joint damage and disability. Although
its exact cause remains unclear, genetic predisposition-(HLA-DRB1) and environmental factors such
as smoking contribute to its development.RA is characterized by chronic synovial inflammation,
primarily in small joints, and, if untreated, can cause irreversible joint damage. While NSAIDs-
DMARDs, and biologics help manage symptoms, a definitive cure is lacking, and treatment
responses vary among patients.
Method: In the first strategy, DCs were modified with a lentiviral vector encoding only the
expression of IDO, which catabolizes tryptophan. In the second approach, DCs were also modified
with a lentiviral vector encoding a fusion protein called CTLA4-KDEL. In the third approach, DCs
were transduced with a lentiviral vector encoding both IDO overexpression and shRNA-mediated
silencing of CD80/CD86 within the same vector construct. Genetically modified DCs were
administered intra-articularly to collagen-induced-RA model mice. Treated RA model were followed
for two weeks. Finally, histopathological examination was performed to evaluate joint inflammation
and tissue damage in the affected joints.
Result and Conclusion: After transduction into DCs, ELISA analysis confirmed upregulation of IDO
in the group expressing the IDO construct and IDO overexpression and shRNA-mediated silencing
of CD80/CD86 within the same vector construct. Flow cytometry showed suppression of surface
markers CD80 and CD86 as a result of CTLA4 transduction, indicating a tolerogenic phenotype. We
demonstrated a significant decrease in the clinical scores of CIA model animals after injection of
DHs, which were given tolerogenic properties using three different strategies. Tolerance-inducing
DCs have exciting potential for the treatment of RA and other autoimmune diseases.