The regulatory roles of glycosphingolipid-enriched lipid rafts in immune systems

Lipid rafts formed by glycosphingolipids (GSLs) on cellular membranes play important roles in innate and adaptive immunity. Lactosylceramide (LacCer) forms lipid rafts on plasma and granular membranes of human neutrophils. These LacCer-enriched lipid rafts bind directly to pathogenic components, such as pathogenic fungi-derived β-glucan and Mycobacteria-derived lipoarabinomannan via carbohydrate-carbohydrate interactions, and mediate innate immune responses to these pathogens. In contrast, a-series and o-series gangliosides form distinct rafts on CD4⁺ and CD8⁺ T cell subsets, respectively, contributing to the respective functions of these cells and stimulating adaptive immune responses through T cell receptors. These findings suggest that gangliosides play indispensable roles in T cell selection and activation. This Review introduces the involvement of GSL-enriched lipid rafts in innate and adaptive immunity.