Abstract
Rheumatoid arthritis is a frequent rheumatic disease and represents a real problem of public health. The current therapies correspond to disease-modifying anti rheumatic drugs (DMARDs) or symptomatic treatments but do not aim to suppress the cause of the disease. Being an autoimmune disease, RA is characterized by the presence of auto reactive immune cells. dendritic cells (DC) are cells professional antigens presenting cells playing a key part in the initiation and modulation of immune responses. Implied in the mechanism of peripheral tolerance, DC are a privileged therapeutic target in autoimmune diseases such as RA. The objectives of my PhD consisted to : -develop an effective cell therapy in the experimental model of collagen-induced arthritis in mice with tolerogenic DC-identify/dissect cellular and molecular mechanism implied in the DC-induced tolerance- optimize/reinforce the immunomodulatory potential of DC in vitro handling.My work allowed the development of an effective and innovative cellular therapeutical approach in an experimental RA model. Indeed, repeated injections of immature DC induce the generation of a regulatory CD49b T cell population presenting strong immunosuppressive capacities. By in vitro handling of DC in order to optimize their tolerogenic capacities , we highlighted the therapeutic potential of several types of DC. This research project made it possible to pose the base of an immunotherapy in RA; However the application of such therapeutic strategies must be considered with precaution and requires investigations before their use in human.