Regulation of Hepatic Inflammation via Macrophage Cell Death

Macrophages are innate immune cells with diverse functions including clearing infectious agents, inducing inflammation and fibrosis, resolving fibrosis, and restoring tissue integrity. Liver macrophages consist of both resident Kupffer cells and infiltrating macrophages. They have heterogeneous highly plastic phenotypes, and they change their phenotypes rapidly in response to a diverse array of signals present in the injured or recovering liver. Cell death by apoptosis, necroptosis, or pyroptosis is a common response of liver macrophages to infectious and toxic insults. At the same time, the uptake of apoptotic and other dead cells, efferocytosis, is mediated by a series of dead cell receptors including MerTK, TIM4, and Stablin-1. These generate a critical signal that determines macrophage phenotype evolution. This review discusses the processes that lead to macrophage apoptosis and efferocytosis, and how these alter the course of liver diseases.