Antigen Presentation and Immunopathology in Heart Failure

Over 26 million people worldwide currently live with heart failure. Improved intervention techniques have significantly increased survival after acute myocardial infarct (MI). However, the regenerative capacity of the adult heart is minimal and myocardial injury frequently initiates the development towards heart failure. Current heart failure drugs cannot restore normal heart function and the major goal is to prolong the patients life and reduce symptoms. Therefore, new strategies to prevent heart failure after MI remain a major therapeutic goal in cardiology. The immune response to heart tissue damage has recently emerged as a crucial contributing factor to functional deterioration after MI. While it has become clear, that the immediate inflammatory response after MI is of critical importance for efficient wound closure and stabilisation of the cardiac wall, a subsequent activation of antigen-specific adaptive immune cells (T and B cells) may lead to autoimmunity, thus persistent immune-mediated damage, against the heart. We therefore believe that targeting the immune response needs to be a critical component of future treatment strategies after MI to prevent heart failure. In this particular project we aim to investigate the immunological pathway of antigen- presentation, which is responsible for the initial induction of self-reactive T cells. The role of this process in the development of autoimmunity against the heart, ongoing tissue damage and eventually functional impairment, is not yet well understood. We will make use of human heart tissue to characterise antigen presentation pathways in various heart diseases, and confirm mechanisms and potential therapeutic relevance in mouse models of ischaemic heart disease. We expect to provide a solid basis for future therapeutic approaches aiming to intervene in the earliest stages of anti-heart autoimmunity in order to prevent heart failure.