Novel resolution-phase macrophages restore post-inflammation tissue homeostasis (360G-Wellcome-087520_Z_08_Z)

While the objective of acute inflammatory resolution is for cell clearance and pro-inflammatory mediator catabolism, tissues must undergo a final process of restoration of tissue homeostasis. This is not only essential for immune recovery but it restores physiology and prepares tissues to mount appropriately-tempered inflammatory responses to future infections or injuries. On this theme, I identified a new population of macrophages found at sites of resolving inflammation that play a central rol e in this process, called resolution-phase (rM) cells. Through the release of unknown prostanoids and/or chemokines, rM trigger the repopulation of innate-type lymphocytes (rLYM), which are crucial for controlling acute inflammatory responses to subsequent infection/injury and curtailing mortality. Therefore, this application proposes to indentify the rM-derived signals that trigger lymphocyte repopulation and elucidate the lymphocyte subpopulation/s responsible for post-resolution protection. A lso, with access to human resolving inflammatory samples I will investigate whether signaling pathways that restore homeostasis in mice also occur in humans. Thus, I believe that tissues revert back to homeostasis after injury/infection in an active manner controlled by soluble mediators and cellular players inherent to pro-resolution processes. By uncovering these novel pro-homeostatic pathways I hope to advance our understanding of chronic inflammatory diseases and susceptibility to infection.