Cholesterol metabolism in innate and adaptive response

It has been long recognized that cholesterol is a critical molecule in mammalian cell biology, primarily for its contribution to the plasma membrane’s composition and its role in assuring proper transmembrane receptor signaling as part of lipid rafts. Efforts have also been made to characterize the cholesterol biosynthetic pathway, cholesterol homeostasis, and cholesterol-derived metabolites in order to gain insights into their dysregulation during metabolic diseases. Despite the central role cholesterol metabolism plays in shaping human health, its regulation during immune activation, such as immune response to pathogens or autoimmune/autoinflammatory diseases, is poorly understood. The immune system is composed of several type of cells with distinct developmental origin, life span, molecular requirements, and gene expressions. It is unclear whether the same array of cholesterol metabolism regulators are equally employed by different immune cells and whether distinct cholesterol metabolites have similar biological consequences in different immune cells. In this review, we will describe how cholesterol metabolism is controlled during the adaptive and the innate immune response and the role for intracellular and extracellular receptors for cholesterol and its derivatives.