Professor Pärt Peterson, University of Tartu
Senior Research Fellow Kai Kisand, University of Tartu
Senior Research Fellow Ana Rebane, University of Tartu
Professor Ola Winqvist, MD, PhD, Karolinska Institutet, Sweden
The purpose of the immune system is to protect the body against diseases meanwhile avoiding damaging of tissues. This is provided by tightly regulated multilevel cooperation of the immune cells. This thesis focuses on dendritic cells; main antigen presenting cells in immune system. Dendritic cells are important both in inducing immune responses and in suppressing harmful reactions. They process foreign material and present it on their cell surface to other immune cells, thereby mediate the action of other immune cells. In cooperation with monocytes, macrophages and other immune cells, dendritic cells help to maintain the immune homeostasis in organisms. In vitro, but also in case of an infection, dendritic cells are rapidly generated in large numbers from monocytes. These monocyte-derived dendritic cells are under going extensive study and are currently the most promising cell type to be used in immunotherapy for cancer and various autoimmune diseases. The aim of this thesis is to study the changes in gene regulation in monocyte differentiation to dendritic cells and to identify differences in monocytes in young and elderly individuals.
We studied gene expression regulation through epigenetic changes in monocyte differentiation. Epigenetics is a study that tries to clarify how limited number of genes can define different cell types without affecting the DNA sequence. In the differentiation of monocytes into macrophages and dendritic cells, several epigenetic changes take place. We described gene expression profiles, histone modifications and microRNA profiles in monocytes, monocyte-derived macrophages and dendritic cells. We showed that gene activity and histone modifications are in good correlation. We also described updated microRNAs expression profiles of dendritic cells and macrophages that revealed several upregulated miRNAs, among others novel miR-511. In addition to differentiation, we also described several differentially methylated CpG sites in monocytes of young and elderly individuals during ageing process that may be useful to better understand the role of epigenetics in ageing and provide new approaches to control inflammatory processes in future.