title: Manipulating membrane lipid profiles to restore T-cell function in autoimmunity.
abstract: Plasma membrane lipid rafts are heterogeneous cholesterol and glycosphingolipid (GSL)-enriched microdomains, within which the tight packing of cholesterol with the saturated-acyl chains of GSLs creates a region of liquid-order relative to the surrounding disordered membrane. Thus lipid rafts govern the lateral mobility and interaction of membrane proteins and regulate a plethora of signal transduction events, including T-cell antigen receptor (TCR) signalling. The pathways regulating homoeostasis of membrane cholesterol and GSLs are tightly controlled and alteration of these metabolic processes coincides with immune cell dysfunction as is evident in atherosclerosis, cancer and autoimmunity. Indeed, membrane lipid composition is emerging as an important factor influencing the ability of cells to respond appropriately to microenvironmental stimuli. Consequently, there is increasing interest in targeting membrane lipids or their metabolic control as a novel therapeutic approach to modulate immune cell behaviour and our recent work demonstrates that this is a promising strategy in T-cells from patients with the autoimmune disease systemic lupus erythematosus (SLE).
authors.affiliation: Centre for Clinical Pharmacology, University College London, The Rayne Building, 5 University Street, London WC1E 6JF, U.K. Centre for Rheumatology, University College London, The Rayne Building, 5 University Street, London WC1E 6JF, U.K.
authors.forename: Kirsty E
authors.initials: KE
authors.lastname: Waddington
authors.affiliation: Centre for Rheumatology, University College London, The Rayne Building, 5 University Street, London WC1E 6JF, U.K. e.jury@ucl.ac.uk.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Jury
mesh_terms: D015551:Autoimmunity; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D008563:Membrane Lipids; D011948:Receptors, Antigen, T-Cell
keywords: T-cells; autoimmunity; cholesterol; glycosphingolipids; lipid rafts; plasma membrane