The metabolic secretome of apoptotic cells influences gene expression programs in neighboring cells

Among the many cells that turnover every day in the body as part of routine homeostasis, more than 90% occurs via apoptosis. Even after a cell commits to apoptosis, it often takes minutes to hours to execute the apoptotic program fully. Here, Kodi Ravichandran and colleagues report that during this interim period when apoptotic cells still maintain plasma membrane integrity, they can communicate with neighboring cells via the regulated release of metabolites. The metabolites are shown to influence gene expression patterns in the surrounding tissue environment, in particular by restricting inflammation and promoting wound healing. A cocktail of select apoptotic metabolites has been shown to reduce disease severity in models of inflammatory arthritis and rejection of lung transplants. This study systematically investigates the generation, release and biological effects (in neighboring cells) of the apoptotic secretome.