title: Peroxisome proliferator-activated receptor γ-regulated cathepsin D is required for lipid antigen presentation by dendritic cells.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Research Center for Molecular Medicine, University of Debrecen, Debrecen 4010, Hungary.
authors.forename: Britt
authors.initials: B
authors.lastname: Nakken
authors.forename: Tamas
authors.initials: T
authors.lastname: Varga
authors.forename: Istvan
authors.initials: I
authors.lastname: Szatmari
authors.forename: Lajos
authors.initials: L
authors.lastname: Szeles
authors.forename: Adrienn
authors.initials: A
authors.lastname: Gyongyosi
authors.forename: Petr A
authors.initials: PA
authors.lastname: Illarionov
authors.forename: Balazs
authors.initials: B
authors.lastname: Dezso
authors.forename: Peter
authors.initials: P
authors.lastname: Gogolak
authors.forename: Eva
authors.initials: E
authors.lastname: Rajnavolgyi
authors.forename: Laszlo
authors.initials: L
authors.lastname: Nagy
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D055610:Antigens, CD1d / Q000276:immunology / Q000378:metabolism; D002402:Cathepsin D / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism / Q000276:immunology; D008074:Lipoproteins / Q000276:immunology / Q000378:metabolism*; D008247:Lysosomes / Q000201:enzymology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D055611:Natural Killer T-Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D047495:PPAR gamma / Q000502:physiology*; D049231:Saposins / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D055610:Antigens, CD1d; C526877:CD1D protein, human; D008074:Lipoproteins; D047495:PPAR gamma; C483345:PSAP protein, human; D049231:Saposins; D002402:Cathepsin D