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Peroxisome proliferator-activated receptor γ-regulated cathepsin D is required for lipid antigen presentation by dendritic cells

Nakken, Britt
Varga, Tamas
Szatmari, Istvan
Gyongyosi, Adrienn
Illarionov, Petr A
Dezso, Balazs
Gogolak, Peter
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Published in The Journal of immunology. 2011, vol. 187, no. 1, p. 240-7
Abstract It is well established that dendritic cells (DCs) take up, process, and present lipid Ags in complex with CD1d molecules to invariant NKT cells. The lipid-activated transcription factor, peroxisome proliferator-activated receptor γ (PPARγ), has previously been shown to regulate CD1d expression in human monocyte-derived DCs, providing a link between lipid metabolism and lipid Ag presentation. We report that PPARγ regulates the expression of a lysosomal protease, cathepsin D (CatD), in human monocyte-derived DCs. Inhibition of CatD specifically reduced the expansion of invariant NKT cells and furthermore resulted in decreased maturation of saposins, a group of lipid transfer proteins required for lysosomal lipid Ag processing and loading. These results reveal a novel mechanism of lipid Ag presentation and identify CatD as a key component of this machinery and firmly place PPARγ as the transcriptional regulator linking lipid metabolism and lipid Ag processing.
Keywords Antigen Presentation/immunologyAntigens, CD1d/immunology/metabolismCathepsin D/biosynthesis/metabolism/physiologyCells, CulturedCoculture TechniquesDendritic Cells/immunology/metabolismHumansLipid Metabolism/immunologyLipoproteins/immunology/metabolismLysosomes/enzymology/metabolismMonocytes/immunology/metabolismNatural Killer T-Cells/enzymology/immunology/metabolismPPAR gamma/physiologySaposins/metabolism/physiologySignal Transduction/immunologyUp-Regulation/immunology
PMID: 21632707
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Research group Groupe Reith Walter (pathologie et immunologie) (282)
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NAKKEN, Britt et al. Peroxisome proliferator-activated receptor γ-regulated cathepsin D is required for lipid antigen presentation by dendritic cells. In: The Journal of immunology, 2011, vol. 187, n° 1, p. 240-7. doi: 10.4049/jimmunol.1002421 https://archive-ouverte.unige.ch/unige:25560

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Deposited on : 2013-01-16

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