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Nat Immunol. 2014 Mar;15(3):248-57. doi: 10.1038/ni.2808. Epub 2014 Jan 19.

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

Author information

1
1] Unit Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, Ghent, Belgium. [2] GROUP-ID Consortium, Ghent University and University Hospital, Ghent, Belgium. [3] Department of Respiratory Medicine, Ghent University, Ghent, Belgium. [4].
2
1] GROUP-ID Consortium, Ghent University and University Hospital, Ghent, Belgium. [2] Unit of Molecular Signal Transduction in Inflammation, VIB Inflammation Research Center, Ghent, Belgium.
3
1] Unit Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, Ghent, Belgium. [2] GROUP-ID Consortium, Ghent University and University Hospital, Ghent, Belgium. [3] Department of Respiratory Medicine, Ghent University, Ghent, Belgium.
4
Microscopy Core Facility, VIB Inflammation Research Center, Ghent, Belgium.
5
Advanced Scientific Research Leaders Development Unit, Gunma University, Gunma, Japan.
6
1] Unit Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, Ghent, Belgium. [2] GROUP-ID Consortium, Ghent University and University Hospital, Ghent, Belgium. [3] Department of Respiratory Medicine, Ghent University, Ghent, Belgium. [4] Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands. [5].

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.

PMID:
24441789
DOI:
10.1038/ni.2808
[Indexed for MEDLINE]
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