The interaction between group 2 innate lymphoid cells and lipid metabolism

Abstract

Abstract Innate lymphoid cells (ILCs) have been found in many tissue sites but are enriched in barrier surfaces such as intestine, lung and skin. They lack antigen-specific receptors yet respond to alarmin signals that are released by tissue, to resemble the cytokine production and effector function of T cells. ILCs play important roles in host defense, tissue repair, autoimmune disorders, inflammation, metabolic homeostasis and more. Recent progress in immunometabolism has highlighted the diverse roles of lipid metabolism in the response and function of immune cells including lymphocytes. But the interaction between ILC2s and lipid metabolism is poorly understood. Our preliminary studies show that, upon activation, intestinal ILC2s significantly upregulate the expression of several genes that are important for cholesterol metabolism. Cholesterol is an essential structural component of mammalian cell membranes and is the precursor for bile acids, vitamin D and steroid hormones. Cholesterol metabolism disorder leads to severe diseases such as hypercholesterolemia, atherosclerosis and diabetes. By using various mouse models and multi-disciplinary experimental approaches, we will study if and how cholesterol regulates the homeostasis, activation and cytokine production of ILC2s and if cholesterol regulation on ILC2s contributes to host defense against helminth infection. We will also investigate if ILC2s in turn modulate lipid, especially cholesterol, metabolism and if ILC2s play any role in hypercholesterolemia or atherosclerosis.