Figure 2.

The processing of engulfed dying cells requires LC3-associated phagocytosis (LAP) and promotes an anti-inflammatory response. Upon engulfment of dying cells, components of the LAP pathway are recruited to dead cell-containing phagosome (or LAPosome). The class III PI3 K complex, comprised of Beclin 1, VPS34, UVRAG, and Rubicon, is critical to the sustained and localized production of PI(3)P at the LAPosome. PI(3)P serves two roles – the recruitment of the downstream LAP machinery (such as ATG5, ATG12, ATG16L, and ATG7) and stabilization of the NOX2 complex for the production of ROS. Rubicon is also required for the stabilization of the NOX2 complex. Both ROS and PI(3)P are required for successful LC3-II decoration of the LAPosome, and LC3-II is required for fusion to the lysosome and maturation of LAPosome. The anti-inflammatory effects of efferocytosis are mediated by the activity of lipid and cholesterol sensors, such as ABCA1, LXR, PPARγ/δ, and PGC-1β, leading to the production of IL-10 and TGFβ, whereas pro-inflammatory mediators, such as IL-12, are actively repressed