The unfolded-protein-response sensor IRE-1 alpha regulates the function of CD8 alpha(+) dendritic cells
| Autor: | Yvan Saeys, Riet De Rycke, Fabiola Osorio, Simon Tavernier, Jessica Vetters, Eef Parthoens, Takao Iwawaki, Philippe Pouliot, Iris Delrue, Bart N. Lambrecht, Eik Hoffmann, Liesbet Martens, Sophie Janssens |
|---|---|
| Přispěvatelé: | Pulmonary Medicine |
| Rok vydání: | 2014 |
| Předmět: |
biology
Endoplasmic reticulum fungi Immunology Antigen presentation Cross-presentation chemical and pharmacologic phenomena Major histocompatibility complex X-Box Binding Protein 1 Cell biology biology.protein Unfolded protein response Immunology and Allergy Antigen-presenting cell Transcription factor |
| Zdroj: | Nature Immunology, 15(3), 248-257. Nature Publishing Group |
| ISSN: | 1529-2908 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|