Cited by 235Endoplasmic Reticulum Stress and DiseaseImmunotherapy and Immune ResponsesIon Channels and Receptors

The unfolded-protein-response sensor IRE-1α regulates the function of CD8α+ dendritic cells

Osorio, Fabiola, Tavernier, Simon J, Hoffmann, Eik, Saeys, Yvan, Martens, Liesbet, Vetters, Jessica, Delrue, Iris, De Rycke, Riet +5 more·2014·Nature Immunology

Abstract

The role of the unfolded protein response (UPR) and endoplasmic reticulum (ER) stress in homeostasis of the immune system is incompletely understood. Here we found that dendritic cells (DCs) constitutively activated the UPR sensor IRE-1α and its target, the transcription factor XBP-1, in the absence of ER stress. Loss of XBP-1 in CD11c+ cells led to defects in phenotype, ER homeostasis and antigen presentation by CD8α+ conventional DCs, yet the closely related CD11b+ DCs were unaffected. Whereas the dysregulated ER in XBP-1-deficient DCs resulted from loss of XBP-1 transcriptional activity, the phenotypic and functional defects resulted from regulated IRE-1α-dependent degradation (RIDD) of mRNAs, including those encoding CD18 integrins and components of the major histocompatibility complex (MHC) class I machinery. Thus, a precisely regulated feedback circuit involving IRE-1α and XBP-1 controls the homeostasis of CD8α+ conventional DCs.

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Crossref · 10.1038/ni.2808

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Authors
Osorio, F., Tavernier, S. J., Hoffmann, E., Saeys, Y., Martens, L., Vetters, J., Delrue, I., De Rycke, R., Parthoens, E., Pouliot, P., Iwawaki, T., Janssens, S., & Lambrecht, B. N.
Affiliations
  • Ghent University Hospital (BE)
  • VIB-UGent Center for Inflammation Research (BE)
  • Gunma University (JP)
Corresponding author
Lambrecht, Bart N
Venue
Nature Immunology
Published
2014-01-19
Volume
15
Issue
3
Pages
248-257
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
OpenAlex
W1530495975
Cited by
235
References
41
Citations by year
2026: 13 · 2025: 10 · 2024: 8 · 2023: 16 · 2022: 25 · 2021: 20 · 2020: 21 · 2019: 21 · 2018: 27 · 2017: 17 · 2016: 17 · 2015: 25 · 2014: 15
FWCI
12.25
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion)
Funders
Japan Society for the Promotion of Science (24390049)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
Keywords
unfolded protein response, IRE1α, XBP1, CD8α+ dendritic cells, endoplasmic reticulum stress, dendritic cell homeostasis, antigen presentation, beta2 integrins, MHC class I, CD11c+ cells, CD11b+ dendritic cells
MeSH terms
Regulatory Factor X Transcription Factors, X-Box Binding Protein 1, Animals, Dendritic Cells, DNA-Binding Proteins, Endoplasmic Reticulum, Endoribonucleases, Homeostasis, Immunohistochemistry, Mice, Inbred C57BL, Microscopy, Electron, Transcription Factors, Immunoblotting, CD8 Antigens, Protein Serine-Threonine Kinases, Antigen Presentation, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Feedback, Physiological, Cross-Priming, Mice, Unfolded Protein Response, Protein Unfolding

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