Aggregates of intracellular crystals or peptides, which lead to various inflammatory diseases, are formed from precursors that activate innate immune cells via the receptor CD36 to produce inflammatory mediators.The findings, reported this week in Nature Immunology, point to CD36 as a potential therapeutic target in autoinflammatory diseases.
Inflammatory diseases, including atherosclerosis, Alzheimer’s disease and type 2 diabetes, are triggered by formation of intracellular crystals or peptide fibrils.Kathryn Moore and colleagues show CD36, a surface receptor, activates two signaling arms in response to oxidized low-density lipoprotein (LDL), a molecule that carries cholesterol in blood. Innate immune cells that express CD36 capture and internalize LDL and its cargo of cholesterol. Accumulation of cholesterol leads to its crystal formation and rupture of intracellular vesicles that triggers inflammasome activation. CD36 forms a signaling complex with other receptors that initiate inflammatory gene expression. Mice lacking CD36 expression fail to develop atherosclerosis when fed high-fat diets.