The transcription factor TFEB acts as a molecular switch that regulates exogenous antigen-presentation pathways

Nat Immunol. 2015 Jul;16(7):729-36. doi: 10.1038/ni.3196. Epub 2015 Jun 1.


Dendritic cells (DCs) can initiate immune responses by presenting exogenous antigens to T cells via both major histocompatibility complex (MHC) class I pathways and MHC class II pathways. Lysosomal activity has an important role in modulating the balance between these two pathways. The transcription factor TFEB regulates lysosomal function by inducing lysosomal activation. Here we report that TFEB expression inhibited the presentation of exogenous antigen by MHC class I while enhancing presentation via MHC class II. TFEB promoted phagosomal acidification and protein degradation. Furthermore, we found that the activation of TFEB was regulated during DC maturation and that phagosomal acidification was impaired in DCs in which the gene encoding TFEB was silenced. Our data indicate that TFEB is a key participant in the differential regulation of the presentation of exogenous antigens by DCs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology*
  • Antigens / immunology*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / immunology*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Cells, Cultured
  • Chlorocebus aethiops
  • Cross-Priming / immunology
  • Flow Cytometry
  • HEK293 Cells
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Hydrogen-Ion Concentration
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Phagosomes / immunology
  • Phagosomes / metabolism
  • Proteolysis
  • RNA Interference / immunology
  • Signal Transduction / immunology*
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism
  • Vero Cells


  • Antigens
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Histocompatibility Antigens Class II
  • Tcfeb protein, mouse