title: High-density lipoprotein phospholipids interfere with dendritic cell Th1 functional maturation.
abstract: Lipoproteins are both lipid carriers in the blood and regulators of essential biological processes. Several studies demonstrated that lipoproteins modified during pathological conditions could alter dendritic cell (DC) maturation. Here the immune function of non-pathological lipoproteins is addressed by analysing their impact on human DC maturation triggered by TLR ligands. Upon TLR4 stimulation, low- and high-density lipoproteins (LDL and HDL) strongly inhibited the ability of DC to induce a Th1 response of T cells, characterized by high levels of IFNγ secretion, whereas the effect of very low-density lipoprotein was subject to variations. HDL also inhibited the Th1 function of DC stimulated by TLR1/2 and TLR2/6 ligands. The phospholipid fraction from HDL retained the inhibitory activity of the lipoprotein. We identified the 1-palmitoyl-2-linoleyl-phosphatidylcholine (PLPC) as one active phospholipid that inhibited the Th1 function of mature DCs whereas the dipalmitoyl-phosphatidylcholine had no significant effect. The treatment of DC by PLPC, 24h before TLR4 stimulation, resulted in reduced activation of NF-κB. This study shows that some HDL phospholipids have a direct immunoregulatory function, by modulating DC ability to activate a Th1 response of T cells.
authors.affiliation: Université de Lyon, France. laure.perrin@inserm.fr
authors.forename: Laure
authors.initials: L
authors.lastname: Perrin-Cocon
authors.forename: Olivier
authors.initials: O
authors.lastname: Diaz
authors.forename: Martine
authors.initials: M
authors.lastname: Carreras
authors.forename: Sandra
authors.initials: S
authors.lastname: Dollet
authors.forename: Aurélie
authors.initials: A
authors.lastname: Guironnet-Paquet
authors.forename: Patrice
authors.initials: P
authors.lastname: André
authors.forename: Vincent
authors.initials: V
authors.lastname: Lotteau
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008075:Lipoproteins, HDL / Q000276:immunology / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000276:immunology / Q000494:pharmacology*; D008079:Lipoproteins, VLDL / Q000276:immunology / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D010713:Phosphatidylcholines / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism; D051216:Toll-Like Receptor 6 / Q000276:immunology / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D016328:NF-kappa B; D010713:Phosphatidylcholines; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495368:TLR6 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; C055402:1-palmitoyl-2-linoleoylphosphatidylcholine; D007371:Interferon-gamma