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

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

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Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA.


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.

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