| First Author | Osorio F | Year | 2014 |
| Journal | Nat Immunol | Volume | 15 |
| Issue | 3 | Pages | 248-57 |
| PubMed ID | 24441789 | Mgi Jnum | J:209368 |
| Mgi Id | MGI:5567027 | Doi | 10.1038/ni.2808 |
| Citation | Osorio F, et al. (2014) The unfolded-protein-response sensor IRE-1alpha regulates the function of CD8alpha+ dendritic cells. Nat Immunol 15(3):248-57 |
| abstractText | 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-1alpha 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 CD8alpha+ 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-1alpha-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-1alpha and XBP-1 controls the homeostasis of CD8alpha+ conventional DCs. |
