Abstract
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.
