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

Author

Listed:
  • Srinath Govindarajan

    (VIB Center for Inflammation Research
    Ghent University Hospital)

  • Djoere Gaublomme

    (VIB Center for Inflammation Research
    Ghent University Hospital)

  • Renée Van der Cruyssen

    (VIB Center for Inflammation Research
    Ghent University Hospital)

  • Eveline Verheugen

    (VIB Center for Inflammation Research
    Ghent University Hospital)

  • Sofie Van Gassen

    (Ghent University
    VIB Center for Inflammation Research)

  • Yvan Saeys

    (Ghent University
    VIB Center for Inflammation Research)

  • Simon Tavernier

    (VIB Center for Inflammation Research
    Ghent University Hospital)

  • Takao Iwawaki

    (Medical Research Institute, Kanazawa Medical University)

  • Yehudi Bloch

    (Ghent University
    VIB Center for Inflammation Research)

  • Savvas. N. Savvides

    (Ghent University
    VIB Center for Inflammation Research)

  • Bart N. Lambrecht

    (VIB Center for Inflammation Research
    Ghent University Hospital
    ErasmusMC)

  • Sophie Janssens

    (VIB Center for Inflammation Research
    Ghent University)

  • Dirk Elewaut

    (VIB Center for Inflammation Research
    Ghent University Hospital)

  • Michael B. Drennan

    (VIB Center for Inflammation Research
    Ghent University Hospital)

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.

Suggested Citation

  • 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. La, 2018. "Stabilization of cytokine mRNAs in iNKT cells requires the serine-threonine kinase IRE1alpha," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07758-x
    DOI: 10.1038/s41467-018-07758-x
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