Abstract
The impact of glycolipids of non-mammalian origin on autoimmune inflammation has become widely recognized. Here we report that the naturally occurring mammalian glycolipids, sulfatide and β-GalCer, affect the differentiation and the quality of antigen presentation by monocyte-derived dendritic cells (DCs). In response to sulfatide and β-GalCer, monocytes develop into immature DCs with higher expression of HLA-DR and CD86 but lower expression of CD80, CD40 and CD1a and lower production of IL-12 compared to non-modulated DCs. Self-glycolipid-modulated DCs responded to lipopolysaccharide (LPS) by changing phenotype but preserved low IL-12 production. Sulfatide, in particular, reduced the capacity of DCs to stimulate autoreactive Glutamic Acid Decarboxylase (GAD65) - specific T cell response and promoted IL-10 production by the GAD65-specific clone. Since sulfatide and β-GalCer induced toll-like receptor (TLR)-mediated signaling, we hypothesize that self-glycolipids deliver a (tolerogenic) polarizing signal to differentiating DCs, facilitating the maintenance of self-tolerance under proinflammatory conditions.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Autoimmunity*
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Cell Differentiation / drug effects*
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Cell Line
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Cells, Cultured
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Cytokines / immunology
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Cytokines / metabolism*
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Dendritic Cells / cytology*
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Dendritic Cells / drug effects*
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Dendritic Cells / metabolism
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Galactosylceramides / pharmacology
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Glycolipids / pharmacology*
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Humans
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Phenotype
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Signal Transduction / drug effects
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Sulfoglycosphingolipids / pharmacology
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T-Lymphocytes / immunology*
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Toll-Like Receptor 2 / metabolism
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Toll-Like Receptor 4 / metabolism
Substances
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Cytokines
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Galactosylceramides
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Glycolipids
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Sulfoglycosphingolipids
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Toll-Like Receptor 2
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Toll-Like Receptor 4
Grants and funding
This work has been supported by the Dutch Diabetes Research Foundation (Expert Center Grant 2008.40.001), the Juvenile Diabetes Research Foundation, the Netherlands Organization for Scientific Research (NWO-VICI, 918.86.611), the European Union (FP7-NAIMIT, number 241447), the Lundbeck Foundation, and the Danish Council for Independent Research | Medical Sciences (number 271-06-0424). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.