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

Nakken, Britt; Varga, Tamas; Szatmari, Istvan; Szeles, Lajos; Gyongyosi, Adrienn; Illarionov, Petr A; Dezso, Balazs; Gogolak, Peter; Rajnavolgyi, Eva; Nagy, Laszlo

doi:10.4049/jimmunol.1002421

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Title		Peroxisome proliferator-activated receptor γ-regulated cathepsin D is required for lipid antigen presentation by dendritic cells
Authors		Nakken, Britt Varga, Tamas Szatmari, Istvan Szeles, Lajos Gyongyosi, Adrienn Illarionov, Petr A Dezso, Balazs Gogolak, Peter Rajnavolgyi, Eva Nagy, Laszlo show all authors [1 - 10]
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/immunology — Antigens, CD1d/immunology/metabolism — Cathepsin D/biosynthesis/metabolism/physiology — Cells, Cultured — Coculture Techniques — Dendritic Cells/immunology/metabolism — Humans — Lipid Metabolism/immunology — Lipoproteins/immunology/metabolism — Lysosomes/enzymology/metabolism — Monocytes/immunology/metabolism — Natural Killer T-Cells/enzymology/immunology/metabolism — PPAR gamma/physiology — Saposins/metabolism/physiology — Signal Transduction/immunology — Up-Regulation/immunology
Identifiers		DOI: 10.4049/jimmunol.1002421 PMID: 21632707
Full text		Article (Published version) (1.7 MB) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Research group		Groupe Reith Walter (pathologie et immunologie) (282)
Citation (ISO format)		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