Innate regulation of the adaptive immune system during autoimmunity

Sammanfattning: Immune activation comprises multiple biological checkpoints to ensure proper and regulated effector functions. Phagocytes such as macrophages, dendritic cells and neutrophils have important functions during inflammation, e.g. clearance of bacterial pathogens. In this thesis, I have studied the regulatory properties of phagocytes and their crosstalk with adaptive immunity has been studied. Their role in the regulation of the adaptive immune system has been investigated at the site of inflammation and in the initiation of the immune response in the secondary lymphoid organs. Different animal models have been used to understand the regulatory properties of phagocytes in the context of autoimmunity and chronic inflammation. We have shown that M2 macrophages can regulate and suppress autoimmunity in murine models of both type 1 diabetes and experimental autoimmune encephalomyelitis (EAE). The M2 macrophages were localized in the targeted organ and had the ability to suppress T cell activation and produce factors that promote wound-healing. Furthermore, we identified TGF β as an important cytokine for the immunosuppressive properties of M2 macrophages, and also a crucial factor in the deactivation of inflammatory monocyte-derived cells during EAE remission. We have also studied the role of neutrophils in the regulation of adaptive immunity in lymph nodes. We generated a neutropenic mouse model and studied how neutrophils interacted with T and B cells during adjuvantinduced inflammation. These studies revealed that neutrophils have an immense role in the activation of B cells and the generation of antibodyproducing plasma cells.