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

Simon J. Tavernier; Fabiola Osorio; Lana Vandersarren; Jessica Vetters; Nele Vanlangenakker; Gert Van Isterdael; Karl Vergote; Riet De Rycke; Eef Parthoens; Lianne Van De Laar; Takao Iwawaki; Juan R. Del Valle; Chih Chi Andrew Hu; Bart N. Lambrecht; Sophie Janssens

doi:10.1038/ncb3518

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

Simon J. Tavernier, Fabiola Osorio, Lana Vandersarren, Jessica Vetters, Nele Vanlangenakker, Gert Van Isterdael, Karl Vergote, Riet De Rycke, Eef Parthoens, Lianne Van De Laar, Takao Iwawaki, Juan R. Del Valle, Chih Chi Andrew Hu, Bart N. Lambrecht, Sophie Janssens

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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.

Original language	English (US)
Pages (from-to)	698-710
Number of pages	13
Journal	Nature Cell Biology
Volume	19
Issue number	6
DOIs	https://doi.org/10.1038/ncb3518
State	Published - May 31 2017

ASJC Scopus subject areas

Cell Biology

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Tavernier, S. J., Osorio, F., Vandersarren, L., Vetters, J., Vanlangenakker, N., Van Isterdael, G., Vergote, K., De Rycke, R., Parthoens, E., Van De Laar, L., Iwawaki, T., Del Valle, J. R., Hu, C. C. A., Lambrecht, B. N., & Janssens, S. (2017). Regulated IRE1-dependent mRNA decay sets the threshold for dendritic cell survival. Nature Cell Biology, 19(6), 698-710. https://doi.org/10.1038/ncb3518

Tavernier, SJ, Osorio, F, Vandersarren, L, Vetters, J, Vanlangenakker, N, Van Isterdael, G, Vergote, K, De Rycke, R, Parthoens, E, Van De Laar, L, Iwawaki, T, Del Valle, JR, Hu, CCA, Lambrecht, BN & Janssens, S 2017, 'Regulated IRE1-dependent mRNA decay sets the threshold for dendritic cell survival', Nature Cell Biology, vol. 19, no. 6, pp. 698-710. https://doi.org/10.1038/ncb3518

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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.",

author = "Tavernier, {Simon J.} and Fabiola Osorio and Lana Vandersarren and Jessica Vetters and Nele Vanlangenakker and {Van Isterdael}, Gert and Karl Vergote and {De Rycke}, Riet and Eef Parthoens and {Van De Laar}, Lianne and Takao Iwawaki and {Del Valle}, {Juan R.} and Hu, {Chih Chi Andrew} and Lambrecht, {Bart N.} and Sophie Janssens",

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AU - Parthoens, Eef

AU - Van De Laar, Lianne

AU - Iwawaki, Takao

AU - Del Valle, Juan R.

AU - Hu, Chih Chi Andrew

AU - Lambrecht, Bart N.

AU - Janssens, Sophie

PY - 2017/5/31

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N2 - 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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Regulated IRE1-dependent mRNA decay sets the threshold for dendritic cell survival

Abstract

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