Tissue Repair: How to Inflame Your Neighbours Pascal Meier, Agnes Banreti  Current Biology  Volume 26, Issue 5, Pages R192-R194 (March 2016) DOI: 10.1016/j.cub.2016.01.033 Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 1 Activation of initiator caspases stimulates a self-amplifying inflammatory response that replaces malfunctioning cells and restores tissue homeostasis. Early in apoptotic signalling, activation of initiator caspases stimulates the transmembrane NADPH oxidase DUOX to produce extracellular reactive oxygen species (ROS) such as H2O2. This attracts and activates macrophages, which in turn signal back to epithelial cells via the TNF-like ligand Eiger (EGR). Binding of Eiger to its receptor Grindelwald (GRND) stimulates JNK activation, both in dying cells as well as in nearby fit/healthy neighbours. In the dying cells, JNK sets in motion a positive feedback loop via the induction of pro-apoptotic molecules, such as HID, an antagonist of inhibitor of apoptosis proteins (IAPs), reinforcing the apoptotic push. Meanwhile, in fit/healthy neighbours activation of JNK and p38 results in the production of mitogens, such as the IL6-like cytokine Unpaired (UPD), which drive proliferation and tissue repair. Under certain conditions, activation of caspases also generates the release of Wingless (WG), Decapentaplegic (DPP) and Spitz (SPI), which subsequently contribute to the coordination of AiP. Current Biology 2016 26, R192-R194DOI: (10.1016/j.cub.2016.01.033) Copyright © 2016 Elsevier Ltd Terms and Conditions