High-density lipoprotein phospholipids interfere with dendritic cell Th1 functional maturation |
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Authors: | Perrin-Cocon Laure Diaz Olivier Carreras Martine Dollet Sandra Guironnet-Paquet Aurélie André Patrice Lotteau Vincent |
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Affiliation: | a Université de Lyon, France b INSERM, U851, 21 Avenue Tony Garnier, Lyon F-69365, France c Hospices Civils de Lyon, Hôpital de la Croix Rousse, Laboratoire de Virologie, France |
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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, 24 h 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. |
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Keywords: | VLDL, very low density lipoprotein IDL, intermediate density lipoprotein LDL, low density lipoprotein HDL, high density lipoprotein oxLDL, oxidized LDL Apo, apolipoprotein DC, dendritic cells IL, interleukin IFN, interferon TLR, Toll-like receptor LPS, lipopolysaccharide PGN, peptidoglycan pIC, poly(I)/poly(C) Pam, Pam3CSK4 MLR, mixed leukocyte reaction LPDS, lipoprotein-deficient foetal calf serum PL, phospholipid TG, triglyceride CE, cholesteryl ester PC, phosphatidylcholine PLPC, 1-palmitoyl-2-linoleyl-phosphatidylcholine POPC, 1-palmitoyl-2-oleoyl-phosphatidyl-choline SLPC, 1-stearoyl-2-linoleyl-phosphatidylcholine PAPC, 1-palmitoyl-2-arachidonoyl-phosphatidylcholine PPPC, dipalmitoyl-phosphatidylcholine LPC, lysophosphatidylcholine LA, linoleic acid HODE, hydroxy-octadecadienoic acid PPAR, peroxisome proliferator-activated receptor EMSA, electrophoretic mobility shift assay |
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