Cell Death Enzyme RIPK3 Found to Trigger Signals from Mitochondria to Natural Killer T Cells, Activating Inflammatory Cytokines; Newly Identified Pathway Influences Both Autoimmunity and Immune Response to Tumors

Scientists at The Scripps Research Institute (TSRI) have discovered a new role for an enzyme involved in cell death. Their study shows how the enzyme, called RIPK3 (image), relays signals between the cell's mitochondria "powerhouses" and the immune system. The new study shows that this crosstalk is important, not only for launching immune responses against tumors, but also for regulating the inflammatory responses that may result in autoimmune diseases. "This finding could be helpful for developing strategies to target cancer and inflammatory diseases," said TSRI Assistant Professor of Immunology Young Jun Kang, who collaborated on the study with the laboratory of TSRI Institute Professor Richard A. Lerner, who is also the Lita Annenberg Hazen Professor of Immunochemistry at TSRI. The study was published online on September 18, 2015 in an open-access article in Nature Communications. The article is titled “Regulation of NKT Cell-Mediated Immune Responses to Tumors and Liver Inflammation by Mitochondrial PGAM5-Drp1 Signaling." Previous studies have shown RIPK3 controls the induction of a type of programmed cell death, called necroptosis, which protects the body from harmful mutations and infections. However, scientists had not fully understood RIPK3's role in the immune system. In this new study, the scientists investigated the role of RIPK3 by studying RIPK3-deficient mice. The research results suggest that RIPK3 regulates the activation of natural killer T cells (NKTs), the immune cells that play dual roles in the development of autoimmune diseases and the destruction of cancers. RIPK3 does not directly cause necroptosis; rather, it regulates the activity of a mitochondrial enzyme (PGAM5) to trigger the expression of inflammatory cytokines in NKTs.
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