Innate regulation of the adaptive immune system during autoimmunity

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.

List of scientific papers

I. Adoptive transfer of immunomodulatory M2 macrophages prevents type I diabetes in NOD mice. Roham Parsa, Pernilla Andresen, Alan Gillett, Sohel Mia, Xing-Mei Zhang, Sofia Mayans, Dan Holmberg, Robert A. Harris Diabetes. 2012 Nov;61(11):2881-92
https://doi.org/10.2337/db11-1635

II. Adoptive transfer of cytokine-induced immunomodulatory adult microglia attenuates experimental autoimmune encephalomyelitis in DBA/1 mice. Xing-Mei Zhang, Harald Lund, Sohel Mia, Roham Parsa, Robert A. Harris Glia. 2014 May;62(5):804-17
https://doi.org/10.1002/glia.22643

III. TGF-beta regulates persistent neuroinflammation by controlling TH1 polarization and ROS production. Roham Parsa, Harald Lund, Ivana Tosevski, Xing-Mei Zhang, Ursula Malipiero, Jan Beckervordersandforth, Doron Merkler, Marco Prinz, Adriano Fontana, Tobias Suter, Robert A. Harris [Manuscript]

IV. Neutrophils regulate local T and B cell activation during adjuvantinduced emergency granulopoiesis. Roham Parsa, Harald Lund, Anna-Maria Georgoudaki, Xing-Mei Zhang, André Ortlieb Guerreiro-Cacais, Andreas Warnecke, Andrew Croxford, Maja Jagodic, Burkhard Becher, Mikael C.I. Karlsson, Robert A. Harris [Manuscript]