Investigation of the Effect of T Lymphocytes Isolated from Multiple Sclerosis Patients on miRNA Profiles in Oligodendrocytes in vitro

Project no. 22973 · Status: Kapanmış (Yayın bekleniyor) · 2022

Summary

Multiple sclerosis (MS) is considered an immune-mediated disease in which the body's immune system attacks the central nervous system (CNS). Many different cells play a role in the abnormal immune response seen in MS. T cells, a key immune cell, are activated in the lymphatic system in MS and enter the CNS via blood vessels, causing inflammation. This inflammation damages neurons, neuronal axons, myelin-producing cells, and myelin itself. Lymphocytes (OLs), which produce the multilayered myelin sheaths that wrap around axons, are considered a crucial cell type in supporting functional recovery in MS patients. Recent studies have shown that the initiation of remyelination is not dependent on axonal signals; rather, peripheral blood cells in the damaged area play a significant role in the progression or cessation of remyelination. However, the molecular basis of this effect is not yet fully understood. In this context, the aim of this project is to investigate the effect of T lymphocytes in peripheral blood on OLs during and after relapses in MS patients. To achieve our goal, peripheral blood samples were first collected from MS patients at two different times (during and after an attack), T lymphocytes were isolated, and these cells were cultured in vitro with OL cells. After cultivation, bioinformatic profiling was performed on the microRNAs (miRNAs) isolated from the OL cells. This revealed the effects of T cells on miRNA expression in OL cells during and after an attack. Based on the differences obtained in this profiling, miR-204-5p was selected as a therapeutic agent and its effects were investigated by applying it to an in vitro demyelination model created using cuprizone. This project identified the T cell-associated miRNAs expressed by OL cells in MS; demonstrated potential miRNAs that could play a role in elucidating the possible effects of these immune cells in CNS diseases; and showcased the potential use of miRNAs in therapeutic approaches. Keywords:Multiple Sclerosis, T lymphocytes, Oligodendrocytes, miRNA

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