Apoptosis (programmed cell death) is a physiological process throughout life as part of development, homeostasis, and pathogenic processes. Apoptosis not only ensures a non-phlogistic removal of apoptotic cells, but is an important mechanism to maintain self-tolerance. The process is characterized by the breakdown of intracellular components such as nucleotides, DNA and intracellular proteins, which otherwise would act as “danger signals”. In addition, apoptotic cells change the decoration of their cell membrane to be recognized, engulfed, and cleared by phagocytes. Decoration of apoptotic cell surfaces is not only modulated by cell-intrinsic mechanisms that induce expression of cell surface molecules, but also involves opsonization with antibodies and complement. Defects in this pathway (e.g., complement deficiencies) result in failure of apoptotic cell clearance and severe autoimmune syndromes in humans. In these patients, chronic inflammation may be driven by insufficient/aberrant clearance of apoptotic cells and/or by phenotypic changes of phagocytic immune cells. During chronic inflammation, danger signals from activated immune cells and necrotic cells may override the immune modulatory capacities of apoptotic signals. We are investigating the signals and mechanisms responsible for uptake of apoptotic cells by phagocytes in inflammatory diseases, with the aim of identifying novel therapeutic concepts to restore homeostatic apoptosis and thereby re-establish tolerance to self.
Modular Antibody Engineering: Antigen binding immunoglobulin Fc CH3 domains as building blocks for bi-specific antibodies (mAb2) Woisetschläger M, Rüker F, Mudde GC, Wozniak-Knopp G, Bauer A and Himmler G. in: Fusion protein technologies for biopharmaceuticals: Applications and Challenges Ed.: Stefan R. Schmidt, Wiley 2013.