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.

Additional Metadata
Persistent URL dx.doi.org/10.1038/ncb3518, hdl.handle.net/1765/108173
Journal Nature Cell Biology
Citation
Tavernier, S.J, Osorio, F, Vandersarren, L. (Lana), Vetters, J, Vanlangenakker, N. (Nele), Van Isterdael, G, … Janssens, S. (2017). Regulated IRE1-dependent mRNA decay sets the threshold for dendritic cell survival. Nature Cell Biology, 19(6), 698–710. doi:10.1038/ncb3518