• Home
  1. Home
  2. Peroxisome proliferator-activated receptor γ-regulated cathepsin D is required for lipid antigen presentation by dendritic cells
Scientific article
English

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

Contributors

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

Published in

The Journal of immunology, vol. 187, no. 1, p. 240-247

Publication date

2011

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

UNIGE affiliation entities

UNIGE research groups

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. 240–247. doi: 10.4049/jimmunol.1002421

Main files (1)

Article (Published version)

Identifiers

Journal ISSN

0022-1767
538views
0downloads

Technical informations

Creation

08/11/2012 13:31:00

First validation

08/11/2012 13:31:00

Update

14/03/2023 19:57:28

Status update

14/03/2023 19:57:27

Last indexation

30/10/2024 08:28:07
All rights reserved by Archive ouverte UNIGE and the University of Geneva
OpenAIRE Indexed & Validated