Systemic and organ-specific Autoimmune Diseases Research Group (AIM)

Description

The research in the AIM group is focused on the pathogenesis of both organ-specific and systemic autoimmune diseases with an emphasis on the role of cells of the myeloid compartment. The next ten years the research will aim at identification of novel biomarkers for these diseases and translation of this knowledge into clinical practice. These biomarkers will be used for establishment of early diagnosis in the pre-symptomatic phase of the disease, monitoring disease progression and prognosis, as novel targets for therapeutic intervention and ultimate prevention of disease development. The identified biomarkers will in combination with novel imaging techniques using specific tracers open a new field of non-invasive medical monitoring with the aim to improve patient care and come to personalized medicine. The current studies focus on: 1\) Abnormalities of monocytes in the circulation in systemic autoimmune diseases 2\) Abnormalities of myeloid cells in the target organs in autoimmune diseases 3\) The role of Interferon type I activation in systemic autoimmune diseases This theme comprises the fundamental aspects of the first steps in the development of an autoimmune disease as well as translational research aiming at the identification of monocyte abnormalities to improve the diagnosis, classification and treatment of autoimmune diseases. The research is performed in mouse models, that spontaneously develop several autoimmune diseases, and is translated into human studies using patient samples. The aim of the research is early detection of the autoimmune diseases. This will allow early intervention, prevention of irreversible damage and ultimately prevention of disease development. Autoimmune diseases have a multifactorial cause involving disturbances in the immune system and in the target organ(s) to which the autoimmune reaction(s) is (are) directed. Dendritic cells (DC) are potent antigen presenting cells capable to activate naïve T cells. Under steady state conditions DC and tissue macrophages pick up auto-antigens in peripheral tissues, for instance in the skin, submandibular glands or in the pancreas and subsequently transport these to the draining lymph nodes to activate T cells. Under steady state conditions the auto-antigen loaded DC and macrophages are in a tolerogenic mode, interacting with T cells in such a way that the induction of autoimmune responses is prevented by a preferential generation of tolerogenic regulator T cells. Under conditions of “danger” (e.g. bacterial or viral infection) DC and macrophages leave their steady tolerogenic state, become aggressive cells and are able to initiate effector T cell responses resulting in the induction of specific immunity and the ultimate elimination of pathogens.