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

Nature Immunology volume 16, pages 729736 (2015) | Download Citation

Abstract

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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Acknowledgements

We thank S. Ferguson (Yale School of Medicine) for the TFEB-EGFP and TFEB(mNLS)-EGFP constructs; A. Iwasaki (Yale School of Medicine) for the gBT and CD11c-DTR mice; W. Shlomchik (Yale School of Medicine) for H-2Kb–SIINFEKL tetramers; R. Medzhitov (Yale School of Medicine) for YM201636, lipoteichoic acid and CpG; R. Leonhadt and J. Grotzke for comments on an earlier version of the manuscript; and the members of the Cresswell laboratory for encouragement and comments. Supported by the Howard Hughes Medical Institute and the US National Institutes of Health (RO1-AI097206 to P.C., and T32 HL007974 to M.S.).

Author information

Affiliations

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

    • Mohammad Samie
    •  & Peter Cresswell

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Contributions

M.S. designed and performed the experiments, analyzed the data and wrote the manuscript; and P.C. designed and supervised the study, analyzed the data and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Peter Cresswell.

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DOI

https://doi.org/10.1038/ni.3196

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