title: High-density lipoprotein attenuates Th1 and th17 autoimmune responses by modulating dendritic cell maturation and function.
abstract: Aberrant levels and function of the potent anti-inflammatory high-density lipoprotein (HDL) and accelerated atherosclerosis have been reported in patients with autoimmune inflammatory diseases. Whether HDL affects the development of an autoimmune response remains elusive. In this study, we used apolipoprotein A-I-deficient (apoA-I(-/-)) mice, characterized by diminished circulating HDL levels, to delineate the role of HDL in autoimmunity. ApoA-I(-/-) mice exhibited increased severity of Ag-induced arthritis compared with wild-type mice, and this was associated with elevated Th1 and Th17 cell reactivity in the draining lymph nodes. Furthermore, reconstituted HDL (rHDL) attenuated IFN-γ and IL-17 secretion by Ag-specific T cells upon stimulation of draining lymph nodes in vitro. The suppressive effects of rHDL were mediated through modulation of dendritic cell (DC) function. Specifically, rHDL-treated DCs demonstrated an immature phenotype characterized by downregulated costimulatory molecules, the release of low amounts of proinflammatory cytokines, and failure to promote T cell proliferation in vitro. The mechanism of action involved the inhibition of NF-κB nuclear translocation and the decrease of Myd88 mRNA levels by rHDL. Finally, modulation of DC function by rHDL was critically dependent on the presence of scavenger receptor class B type I and ATP Binding Cassette Transporter A1, but not the ATP Binding Cassette Transporter G1. These findings reveal a novel role of HDL in the regulation of adaptive inflammatory responses through suppression of DC function that could be exploited therapeutically in autoimmune inflammatory diseases.
authors: Laboratory of Biochemistry, Department of Basic Sciences, University of Crete Medical School, 71003 Heraklion, Crete, Greece; Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, 70013 Heraklion, Crete, Greece;
authors: Ioanna
authors: I
authors: Tiniakou
authors: Department of Pathology, University of Crete Medical School, 71003 Heraklion, Crete, Greece;
authors: Elias
authors: E
authors: Drakos
authors: Department of Pathology, University of Crete Medical School, 71003 Heraklion, Crete, Greece;
authors: Vaios
authors: V
authors: Sinatkas
authors: Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, 2333 Leiden, the Netherlands;
authors: Miranda
authors: M
authors: Van Eck
authors: Laboratory of Biochemistry, Department of Basic Sciences, University of Crete Medical School, 71003 Heraklion, Crete, Greece; Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118; and.
authors: Vassilis I
authors: VI
authors: Zannis
authors: Biomedical Research Foundation, Academy of Athens, 11527 Athens, Greece.
authors: Dimitrios
authors: D
authors: Boumpas
authors: Biomedical Research Foundation, Academy of Athens, 11527 Athens, Greece kardasis@imbb.forth.gr pverginis@bioacademy.gr.
authors: Panayotis
authors: P
authors: Verginis
authors: Laboratory of Biochemistry, Department of Basic Sciences, University of Crete Medical School, 71003 Heraklion, Crete, Greece; Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, 70013 Heraklion, Crete, Greece; kardasis@imbb.forth.gr pverginis@bioacademy.gr.
authors: Dimitris
authors: D
authors: Kardassis
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D008075:Lipoproteins, HDL / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D008075:Lipoproteins, HDL