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J Immunol. 2015 May 15;194(10):4676-87. doi: 10.4049/jimmunol.1402870. Epub 2015 Apr 13.

High-density lipoprotein attenuates Th1 and th17 autoimmune responses by modulating dendritic cell maturation and function.

Author information

1
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;
2
Department of Pathology, University of Crete Medical School, 71003 Heraklion, Crete, Greece;
3
Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, 2333 Leiden, the Netherlands;
4
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.
5
Biomedical Research Foundation, Academy of Athens, 11527 Athens, Greece.
6
Biomedical Research Foundation, Academy of Athens, 11527 Athens, Greece kardasis@imbb.forth.gr pverginis@bioacademy.gr.
7
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.

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.

PMID:
25870241
PMCID:
PMC4417411
DOI:
10.4049/jimmunol.1402870
[Indexed for MEDLINE]
Free PMC Article

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