Efferocytosis: Gateway for tissue resolution

Following a central nervous system (CNS) injury including stroke, inflammation is a complex but crucial part of the body's response. Although the extent of inflammation correlates with stroke severity, anti-inflammatory drugs have shown limited success in clinical trials. In fact, blocking the entry of inflammatory cells, such as monocytes, into the brain hindered the recovery process. This highlights the dual role of these immune cells, which differentiate into monocyte-derived macrophages (M-Mϕ) at the site of injury. These M-Mϕ are essential for both initiating and resolving the inflammatory response. The ability of the macrophages to switch their function and phenotype, from inflammatory to pro-resolving, renders them as a promising therapeutic target for inflammatory diseases. A critical step in this resolution is efferocytosis: the orchestrated clearance of apoptotic cells by phagocytes. This process is mediated by interactions between cellular danger signals and pattern recognition receptors (PRRs), which ultimately trigger the macrophage's shift toward a resolving phenotype. This review will delve into the roles of PRRs and macrophage phenotypic changes, the importance of continuous efferocytosis, and the potential of enhancing efferocytosis as a therapeutic strategy for inflammatory diseases with a focus on cerebral ischemia.