Dying cells in the body can keep the immune system in check, thus preventing unwanted immune responses against the body's own tissues. Scientists of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have now identified a receptor on immune cells that activates this protective mechanism. This prevents dangerous autoimmune reactions in which the immune system is directed against the body's own structures, as the researchers have now been able to show in mice and human cells.
Billions of cells die every day in the human body. This occurs as part of a highly regulated process called apoptosis or programmed cell death. The dying cells confront the immune system with large amounts of proteins, which ought to activate an immune response, but the apoptotic cells seem to actively suppress the immune system so that it does not attack the body's own tissues. "We began wondering many years ago what kind of protective mechanism prevents autoimmune reactions – the body attacking its own tissues – when cells in the immune system, such as dendritic cells, take up the remains of the dead cells," Peter Krammer, an immunologist at the German Cancer Research Center (DKFZ), remarked.
Krammer, his colleague Heiko Weyd, and their team recently found an answer to the question: As soon as apoptosis is triggered, the dying cells transport proteins from the annexin family to the cell surface. The annexins act like a stop signal for the cells of the immune system and prevent an immune response from being triggered.
Kevin Bode from Krammer's department has now identified the dectin-1 protein as the annexin-binding receptor on the surface of dendritic cells: Dectin-1 recognizes the annexins and triggers a signaling pathway in dendritic cells that ultimately suppresses the immune response.
Mice that do not have any dectin-1 on the surface of their dendritic cells showed a stronger immune response to dying, apoptotic cells. Moreover, the mice without dectin-1 developed signs of autoimmune diseases in old age.
Research Article: Kevin Bode, Fatmire Bujupi, Corinna Link, Tobias Hein, Stephanie Zimmermann, Diluka Peiris, Vincent Jaquet, Bernd Lepenies, Heiko Weyd and Peter H. Krammer: Dectin-1 binding to annexins on apoptotic cells induces peripheral immune tolerance via NADPH oxidase-2. CELL Reports DOI: 10.1016/j.celrep.2019.11.086