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PLoS One. 2012;7(12):e52639. doi: 10.1371/journal.pone.0052639. Epub 2012 Dec 20.

Self-glycolipids modulate dendritic cells changing the cytokine profiles of committed autoreactive T cells.

Author information

1
Bartholin Instituttet, Rigshospitalet, Copenhagen, Denmark. buschard@dadlnet.dk

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.

PMID:
23285123
PMCID:
PMC3527583
DOI:
10.1371/journal.pone.0052639
[Indexed for MEDLINE]
Free PMC Article

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