Lipid metabolic reprogramming in immune regulation and chronic inflammatory diseases

Abstract

Immune cells undergo substantial metabolic rewiring during differentiation and activation to satisfy the energy demands of an appropriate immune response. Lipids serve as energy sources and function as essential components of cellular membranes and signaling molecules. Recent studies have revealed that reprogramming of lipid metabolism, including lipid uptake, de novo synthesis of cholesterol and fatty acids, and fatty acid oxidation, leads to dynamic alterations in the quantity and quality of intracellular lipids. These metabolic changes play crucial roles in shaping immune cell functions, promoting anti-inflammatory responses, and facilitating the resolution of inflammation. Conversely, dysregulation of lipid metabolism can result in immune cell dysfunction, contributing to the onset and progression of chronic inflammatory diseases such as autoimmune diseases and metabolic syndrome. Notably, cholesterol and fatty acid metabolism influence immune responses by modulating membrane lipid composition and downstream inflammatory signaling. Given these insights, targeting lipid metabolism has emerged as a promising therapeutic approach for restoring immune homeostasis and treating chronic inflammatory diseases.