Apoptotic cell-derived membrane microparticles: molecular characterization, immunmodulatory activity and their role in the pathogenesis of systemic lupus erythematosus

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Research on extracellular vesicles represents a very young field in science. To date, membrane microparticles are discussed to mediate intercellular communication or act as regulators of immune responses. However, the molecular composition of these vesicles and the interaction of membrane microparticles with responder cells are only partially understood. During the last years our group and others could provide evidence that membrane vesicles released from apoptotic cells differ from those released from activated/viable cells. Further, these subcellular vesicles have been shown to modulate the function of different responder cells. A role of microparticles in the pathogenesis of autoimmune diseases has also been discussed. We have previously shown, that autoantigens, which are involved in the pathogenesis of systemic lupus erythematosus (SLE) accumulate within isolated microparticles of apoptotic cells. Beside this we were able to detect HMGB1 within apoptotic cell derived microparticles. Only recently, the exchange of genetic information via released membrane vesicles has been discussed. Based on our previous work we want to address the following points within this project.1) The molecular composition of isolated membrane microparticles will be further investigated. Here, we want to compare isolated membrane microparticles obtained from healthy individuals and SLE patients.2) The interactions between membrane microparticles and antigen presenting cells (i.e. dendritic cells) will be characterized.3) After stimulation with membrane microparticles we will analyze the interactions between antigen presenting cells and their responder cells (i.e. interactions between dendritic cells and lymphocytes)4) An in vivo model will be established to investigate the immunomodulatory effects of isolated membrane microparticles.