Journal
NATURE IMMUNOLOGY
Volume 15, Issue 3, Pages 248-257Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2808
Keywords
-
Categories
Funding
- European Research Council
- European Union Seventh Framework Programme
- Fonds Wetenschappelijk Onderzoek Vlaanderen program
- Ghent University
- Marie Curie Actions
- Federation of European Biochemical Societies
- Agentschap voor Innovatie door Wetenschap en Techniek
- Grants-in-Aid for Scientific Research [24390049] Funding Source: KAKEN
Ask authors/readers for more resources
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-1 alpha 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 CD8 alpha(+) 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-1 alpha-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-1 alpha and XBP-1 controls the homeostasis of CD8 alpha(+) conventional DCs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available