LXR directly regulates glycosphingolipid synthesis and affects human CD4+ T cell function

Significance This work shows that the liver X receptor (LXR) regulates glycosphingolipid biosynthesis expression in primary human T cells, thereby influencing T cell plasma membrane lipid composition, subsequent immune synapse formation, and T cell receptor-mediated signaling and function. Furthermore, we show LXR actions are differentially regulated in functional T cell subsets, supporting an important role for lipid metabolism in human T cell homeostasis. This new mode of action for LXR could be of therapeutic relevance to disorders characterized by defects in T cell signaling and metabolism, including autoimmune and neurodegenerative diseases, cardiovascular disease, and cancer.