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

J Immunol. 2011 Jul 1;187(1):240-7. doi: 10.4049/jimmunol.1002421. Epub 2011 Jun 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / immunology*
  • Antigens, CD1d / immunology
  • Antigens, CD1d / metabolism
  • Cathepsin D / biosynthesis
  • Cathepsin D / metabolism*
  • Cathepsin D / physiology
  • Cells, Cultured
  • Coculture Techniques
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Humans
  • Lipid Metabolism / immunology
  • Lipoproteins / immunology
  • Lipoproteins / metabolism*
  • Lysosomes / enzymology
  • Lysosomes / metabolism
  • Monocytes / immunology
  • Monocytes / metabolism
  • Natural Killer T-Cells / enzymology
  • Natural Killer T-Cells / immunology
  • Natural Killer T-Cells / metabolism
  • PPAR gamma / physiology*
  • Saposins / metabolism
  • Saposins / physiology
  • Signal Transduction / immunology
  • Up-Regulation / immunology


  • Antigens, CD1d
  • CD1D protein, human
  • Lipoproteins
  • PPAR gamma
  • PSAP protein, human
  • Saposins
  • Cathepsin D