出版社：American Society for Biochemistry and Molecular Biology
摘要：Polyunsaturated fatty acids, including docosahexaenoic acid(DHA, 22:6n-3), modulate immune responses and exert beneficialimmunosuppressive effects, but the molecular mechanisms inhibitingT-cell activation are not yet elucidated. Lipid rafts have beenshown to play an important role in the compartmentalizationand modulation of cell signaling. We investigated the role ofDHA in modulating the lipid composition in lipid rafts and membranesubdomain distribution of interleukin-2 (IL-2) receptor signalingmolecules. We found that DHA altered lipid components of raftsand modified the IL-2-induced Janus kinase-signal transducerand activator of transcription (STAT) signaling pathway by partiallydisplacing IL-2 receptors from lipid rafts. We fractionatedplasma membrane subcellular compartments and discovered thatcertain amounts of STAT5a and STAT5b existed in detergent-resistantplasma membrane fractions of T-cells. After DHA treatment, STAT5aand STAT5b were not detected in lipid raft fractions and werelocated in detergent-soluble fractions.
These data demonstrate for the first time that DHA alters thelipid composition of membrane microdomains and suppresses IL-2receptor signaling in T-cells. Thus, our data provide evidencefor a functional modification in lipid rafts by DHA treatmentand explain PUFA-mediated immunosuppressive effects.Abbreviations: DHA, docosahexaenoic acid, 22:6n-3; EPA, eicosapentaenoic acid; IL, interleukin; JAK, Janus kinase; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PI, phosphatidylinositol; PS, phosphatidylserine; SM, sphingomyelin; STAT, signal transducer and activator of transcription
Supplementary key words polyunsaturated fatty acids • lipid rafts • fatty acid composition • Janus kinase-signal transducer and activator of transcription signaling pathway
