Title

The transcription factor XBP-1 is essential for the development and survival of dendritic cells

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences

Date

9-19-2007

Document Type

Article

Medical Subject Headings

Animals; Cell Differentiation; Cell Survival; Cells, Cultured; DNA-Binding Proteins; Dendritic Cells; Endoplasmic Reticulum; Lymphocytes; Mice; Mice, Knockout; Microscopy, Electron; Sensitivity and Specificity; Transcription Factors

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Dendritic cells (DCs) play a critical role in the initiation, maintenance, and resolution of an immune response. DC survival is tightly controlled by extracellular stimuli such as cytokines and Toll-like receptor (TLR) signaling, but the intracellular events that translate such extracellular stimuli into life or death for the DC remain poorly understood. The endoplasmic reticulum (ER) stress, or unfolded protein response (UPR), is a signaling pathway that is activated when unfolded proteins accumulate in the ER. The most conserved arm of the UPR involves IRE1alpha, an ER transmembrane kinase and endoribonuclease that activates the transcription factor XBP-1 to maintain ER homeostasis and prevent activation of cell death pathways caused by sustained ER stress. We report that XBP-1 is essential for DC development and survival. Lymphoid chimeras lacking XBP-1 possessed decreased numbers of both conventional and plasmacytoid DCs with reduced survival both at baseline and in response to TLR signaling. Overexpression of XBP-1 in hematopoietic progenitors rescued and enhanced DC development. Remarkably, in contrast to other cell types we have examined, the XBP-1 pathway was constitutively activated in immature DCs.

Rights and Permissions

Citation: J Exp Med. 2007 Oct 1;204(10):2267-75. Epub 2007 Sep 17. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

17875675