When autologous chromatin becomes a foe

摘要

Apoptotic cells are recognized and cleared by the innate immune system. This process severely influences the outcome of several important functions of the latter. Apoptotic cells serve as sources for autoantigens employed by immature dendritic cells to maintain tolerance, excellent to prevent autoimmune diseases disastrous when this causes tumor tolerance. Apoptotic cells orchestrate healing and repopulation of the tissues, in which they died, again advantageous during wound healing and in the resolution phase of infections but a disaster after tumor reducing therapies. Many highly pathogenic microorganisms and viruses mimic changes of apoptotic cells like exposure of phosphatidyl serine and abuse their immune silencing signals to escape immune detection and eradication. If autologous chromatin is not properly cleared it is misinterpreted by the immune system as virus and causes the secretion by phagocytes of type-1 interferons. The continuous presence of these cytokines challenges tolerance and leads to SLE-like autoimmunity.