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PMID: 17875675 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

The Journal of experimental medicine ·Vol. 204 ·No. 10 ·2007-10-01 ·Pages 2267-75

Iwakoshi NN, Pypaert M, Glimcher LH

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.

MeSH Terms
Animals Cell Differentiation/immunology Cell Survival Cells, Cultured DNA-Binding Proteins/deficiency,genetics,immunology,metabolism Dendritic Cells/cytology,immunology,metabolism Endoplasmic Reticulum/immunology,metabolism Lymphocytes/immunology,metabolism Mice Mice, Knockout Microscopy, Electron Regulatory Factor X Transcription Factors Sensitivity and Specificity Transcription Factors/deficiency,genetics,immunology,metabolism X-Box Binding Protein 1
Chemicals
DNA-Binding Proteins Regulatory Factor X Transcription Factors Transcription Factors X-Box Binding Protein 1 Xbp1 protein, mouse
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Iwakoshi Neal N
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Pypaert Marc
Glimcher Laurie H
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20070525
Published
2007-10-01
Epub
2007-00-17
Pages
2267-75
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2118458
Subset
IM
Grants
NIAID NIH HHS · P01 AI056296 · United States
NIAID NIH HHS · R01 AI032412 · United States
NIAID NIH HHS · AI32412 · United States
NIAID NIH HHS · AI56296 · United States
External Links
PubMed source DOI: 10.1084/jem.20070525 PMC Full Text View journal details
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