title: Self-glycolipids modulate dendritic cells changing the cytokine profiles of committed autoreactive T cells.
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.
authors.affiliation: Bartholin Instituttet, Rigshospitalet, Copenhagen, Denmark. buschard@dadlnet.dk
authors.forename: Karsten
authors.initials: K
authors.lastname: Buschard
authors.forename: Jan-Eric
authors.initials: JE
authors.lastname: Månsson
authors.forename: Bart O
authors.initials: BO
authors.lastname: Roep
authors.forename: Tatjana
authors.initials: T
authors.lastname: Nikolic
mesh_terms: D015551:Autoimmunity; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D005699:Galactosylceramides / Q000494:pharmacology; D006017:Glycolipids / Q000494:pharmacology*; D006801:Humans; D010641:Phenotype; D015398:Signal Transduction / Q000187:drug effects; D013433:Sulfoglycosphingolipids / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D016207:Cytokines; D005699:Galactosylceramides; D006017:Glycolipids; D013433:Sulfoglycosphingolipids; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4