The unfolded-protein-response sensor IRE-1α regulates the function of CD8α+ dendritic cells
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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Knockout of the UPR transcription factor XBP1 causes upregulation of SHMT2 in dendritic cells.
“Additionally, knockout of a key UPR transcription factor XBP1 caused an upregulation of SHMT2 in dendritic cells.219”
From A review of small-molecule inhibitors of one-carbon enzymes: SHMT2 and MTHFD2 in the spotlight (2021) · cites this paper as [219]
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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
- ORCID
- 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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