The unfolded-protein-response sensor IRE-1 alpha regulates the function of CD8 alpha(+) dendritic cells

Osorio, F; Tavernier, SJ; Hoffmann, E; Saeys Y.; Martens L.; Vetters, J; Delrue, I; De Rycke R.; Parthoens E.; Pouliot, P; Iwawaki T.; Janssens S.; Lambrecht, BN

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-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.

Más información

Título según WOS: The unfolded-protein-response sensor IRE-1 alpha regulates the function of CD8 alpha(+) dendritic cells
Título de la Revista: NATURE IMMUNOLOGY
Volumen: 15
Número: 3
Editorial: NATURE PORTFOLIO
Fecha de publicación: 2014
Página de inicio: 248
Página final: 257
Idioma: English
DOI:

10.1038/ni.2808

Notas: ISI