2. Academic Validation
  3. Regulated IRE1-dependent mRNA decay sets the threshold for dendritic cell survival

Regulated IRE1-dependent mRNA decay sets the threshold for dendritic cell survival

  • Nat Cell Biol. 2017 Jun;19(6):698-710. doi: 10.1038/ncb3518.
Simon J Tavernier 1 2 3,  Fabiola Osorio 1 2 3,  Lana Vandersarren 1 2 3,  Jessica Vetters 1 2 3,  Nele Vanlangenakker 1 2 3,  Gert Van Isterdael 1 2 4,  Karl Vergote 1 2 3,  Riet De Rycke 4 5,  Eef Parthoens 4 5,  Lianne van de Laar 1 3 6,  Takao Iwawaki 7,  Juan R Del Valle 8,  Chih-Chi Andrew Hu 9,  Bart N Lambrecht 1 2 3 10,  Sophie Janssens 1 2 3
Affiliations

Affiliations

  • 1 Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, 9052 Ghent, Belgium.
  • 2 GROUP-ID Consortium, Ghent University and University Hospital, 9000 Ghent, Belgium.
  • 3 Department of Internal Medicine, Ghent University, 9000 Ghent, Belgium.
  • 4 VIB Bioimaging Core, 9052 Ghent, Belgium.
  • 5 Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium.
  • 6 Department of Rheumatology &Clinical Immunology, Laboratory of Translational Immunology, Utrecht University Medical Center, 3584 Utrecht, The Netherlands.
  • 7 Division of Cell Medicine, Department of Life Science, Medical Research Institute, Kanazawa Medical University, 920-0856 Kanazawa, Japan.
  • 8 Department of Chemistry, University of South Florida, Tampa, Florida 33620, USA.
  • 9 Department of Translational Tumor Immunology, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
  • 10 Department of Pulmonary Medicine, ErasmusMC, 2040 Rotterdam, The Netherlands.
PMID: 28459443 DOI: 10.1038/ncb3518
Abstract

The IRE1-XBP1 signalling pathway is part of a cellular programme that protects against endoplasmic reticulum (ER) stress, but also controls development and survival of immune cells. Loss of XBP1 in splenic type 1 conventional dendritic cells (cDC1s) results in functional alterations without affecting cell survival. However, in mucosal cDC1s, loss of XBP1 impaired survival in a tissue-specific manner-while lung cDC1s die, intestinal cDC1s survive. This was not caused by differential activation of ER stress cell-death regulators CHOP or JNK. Rather, survival of intestinal cDC1s was associated with their ability to shut down protein synthesis through a protective integrated stress response and their marked increase in regulated IRE1-dependent messenger RNA decay. Furthermore, loss of IRE1 endonuclease on top of XBP1 led to cDC1 loss in the intestine. Thus, mucosal DCs differentially mount ATF4- and IRE1-dependent adaptive mechanisms to survive in the face of ER stress.

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