Self-Glycolipids Modulate Dendritic Cells Changing the Cytokine Profiles of Committed Autoreactive T Cells

• 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 beta-GalCer, affect the differentiation and the quality of antigen presentation by monocyte-derived dendritic cells (DCs). In response to sulfatide and beta-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 beta-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.

Ämnesord

NATURVETENSKAP  -- Annan naturvetenskap (hsv//swe)

NATURAL SCIENCES  -- Other Natural Sciences (hsv//eng)

Nyckelord

dependent diabetes-mellitus

ii nkt cells

beta-cells

insulin epitope

nod mice

sulfatide

galactosylceramide

prevents

autoimmunity

pathogenesis

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