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Activation of PPARgamma
specifies a dendritic cell subtype capable of enhanced induction of iNKT
cell expansion.
Szatmari I, Gogolak P, Im JS, Dezso
B, Rajnavolgyi E, Nagy L.
Department of Biochemistry and
Molecular Biology, Research Center for Molecular Medicine, University of
Debrecen, Medical and Health Science Center, Nagyerdei krt. 98, H-4012,
Hungary.
Little is known of the transcriptional events
controlling the differentiation and function of dendritic cells (DC). We
found that the ligand-activated transcription factor Peroxisome
Proliferator Activated Receptor gamma (PPARgamma) is immediately
upregulated after the induction of monocyte-derived DC differentiation.
Activation of PPARgamma changed the expression pattern of cell surface
receptors and enhanced the internalizing activity of DC. Unexpectedly,
we found that CD1 glycoproteins, a class of molecules responsible for
the presentation of self and foreign modified lipids, were coordinately
regulated by PPARgamma activation. CD1a levels were reduced, while CD1d
expression was induced. Enhanced expression of CD1d was coupled to the
selective induction of invariant natural-killer T cell (iNKT cell)
proliferation in the presence of alpha-GalCer. These results suggest
that PPARgamma orchestrates a transcriptional response leading to the
development of a DC subtype with increased internalizing capacity,
efficient lipid presentation, and the augmented potential to activate
iNKT cells.
PMID: 15345223 [PubMed - indexed for MEDLINE]
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