PTEN regulates autoimmunity by T-cell check point inhibition

The incidence of autoimmune diseases is constantly rising in the western world. Hence there is a need for a better understanding of the molecular basis for the initiation and the progression of diseases such as rheumatoid arthritis and multiple sclerosis. Within this proposal we aim to elucidate the impact of signaling pathways in multiple sclerosis. In a previous study we could demonstrate that lack of protective signal transduction in leukocytes efficiently protects mice from onset as well as progression of multiple sclerosis. Therefore one of our goals is to address the question which molecules and which cell types are involved in the beneficial outcome. Taken together our proposed study will shed light on the molecular mechanisms in autoimmunity and might therefore provide the basis for the development of therapeutic strategies in the treatment of autoimmune diseases.

Macrophages are a relevant innate immune cells in tissue homeostasis. One of their most important features is plasticity, which gives macrophages the opportunity to react rapidly to drastic changes in the tissue microenvironment. However thus processes need to be tightly regulated. In particular in autoimmune diseases macrophages may either contribute to the severity of disease or on the other hand ameliorate the course of disease. Hence, macrophages function as a double edged sword. Therefore it is vital to understand the different activation states macrophages can acquire and how this is controlled on a cellular level. One of the pathways important in this respect is the PI3K/PTEN signaling pathway. With this project we wanted to shed some light on the role of these relevant signaling molecules in macrophage plasticity in health and disease.