Stabilization of cytokine mRNAs in iNKT cells requires the serine-threonine kinase IRE1alpha

Srinath Govindarajan, Djoere Gaublomme, Renée Van der Cruyssen, Eveline Verheugen, Sofie Van Gassen, Yvan Saeys, Simon Tavernier, Takao Iwawaki, Yehudi Bloch, Savvas. N. Savvides, Bart N. Lambrecht, Sophie Janssens, Dirk Elewaut () and Michael B. Drennan
Additional contact information
Srinath Govindarajan: VIB Center for Inflammation Research
Djoere Gaublomme: VIB Center for Inflammation Research
Renée Van der Cruyssen: VIB Center for Inflammation Research
Eveline Verheugen: VIB Center for Inflammation Research
Sofie Van Gassen: Ghent University
Yvan Saeys: Ghent University
Simon Tavernier: VIB Center for Inflammation Research
Takao Iwawaki: Medical Research Institute, Kanazawa Medical University
Yehudi Bloch: Ghent University
Savvas. N. Savvides: Ghent University
Bart N. Lambrecht: VIB Center for Inflammation Research
Sophie Janssens: VIB Center for Inflammation Research
Dirk Elewaut: VIB Center for Inflammation Research
Michael B. Drennan: VIB Center for Inflammation Research

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Activated invariant natural killer T (iNKT) cells rapidly produce large amounts of cytokines, but how cytokine mRNAs are induced, stabilized and mobilized following iNKT activation is still unclear. Here we show that an endoplasmic reticulum stress sensor, inositol-requiring enzyme 1α (IRE1α), links key cellular processes required for iNKT cell effector functions in specific iNKT subsets, in which TCR-dependent activation of IRE1α is associated with downstream activation of p38 MAPK and the stabilization of preformed cytokine mRNAs. Importantly, genetic deletion of IRE1α in iNKT cells reduces cytokine production and protects mice from oxazolone colitis. We therefore propose that an IRE1α-dependent signaling cascade couples constitutive cytokine mRNA expression to the rapid induction of cytokine secretion and effector functions in activated iNKT cells.

Date: 2018
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DOI: 10.1038/s41467-018-07758-x

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