Docosahexaenoic Acid Changes Lipid Composition and IL-2 Receptor Signaling in Membrane Rafts Running Title: DHA changes Rafts

Polyunsaturated fatty acids (PUFAs) including docosahexaenoic acid (DHA; 22:6 n-3) modulate immune responses and exert beneficial immunosuppressive effects, but the molecular mechanisms inhibiting T cell activation are not yet elucidated. Lipid rafts have been shown to play an important role in the compartmentalization and modulation of cell signaling. We investigate the role of DHA in modulating the lipid composition in lipid rafts and membrane subdomain distribution of IL-2 receptor signaling molecules. We found that DHA altered lipid components of rafts and modified IL-2-induced JAK-STAT signaling pathway through partially displacing IL-2 receptors from lipid rafts. We fractioned plasma membrane subcellular compartments and discovered that certain amounts of STAT5a and STAT5b existed in detergent-resistant plasma membrane fractions of T cells. After DHA treatment, STAT5a and STAT5b were not detected in lipid raft fractions and located in detergent-soluble fractions. These data demonstrate for the first time that DHA alters lipid composition of membrane microdomains and suppresses the IL-2 receptor signaling in T cells. Thus, our data provide some evidences for a functional modification in lipid rafts by DHA treatment and explain PUFAs-mediated immunosuppressive effects. Supplementary key words: Polyunsaurated fatty acids (PUFAs), docosahexaenoic acid (DHA), Lipid rafts, Fatty acid composition, JAK-STAT signaling pathway. 2 by gest, on O cber 4, 2017 w w w .j.org D ow nladed fom