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.,
Nature Cell Biology
Department of Pulmonology

Tavernier, S., 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