The fate of cells Interference and study of macrophage differentiation and activation

The immune system and its cells are important in host defence but also play a role in many acute and chronic diseases. Important cells of the immune system are the macrophages. Macrophages are phagocytic cells with a wide variety of functions including clearing up debris, cytokine production, activation, and regulation of other immune cells, etc. Macrophages originate, among other sources, from circulating monocytes. Upon entering tissue and monocytes encounter different differentiation factors like M-CSF or GM-CSF become mature macrophages. This differentiation process from monocytes to macrophages is regulated by many factors, including epigenetic processes and local mediators present in the tissues. In this thesis, the process of differentiation from monocytes to macrophages and the obtained macrophage’s phenotype, depending on the presence of different mediators (M-CSF, GM-CSF and IFNγ) is explored. Furthermore, the regulation of the differentiation by epigenetics is assessed by using small molecules inhibitors in the context of inflammatory diseases like rheumatoid arthritis or cardiovascular disease.