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

Srinath Govindarajan (UGent) , Djoere Gaublomme (UGent) , Renée Van der Cruyssen (UGent) , Eveline Verheugen (UGent) , Sofie Van Gassen (UGent) , Yvan Saeys (UGent) , Simon Tavernier (UGent) , Takao Iwawaki, Yehudi Bloch (UGent) , Savvas Savvides (UGent) , et al.
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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 1 alpha (IRE1 alpha), links key cellular processes required for iNKT cell effector functions in specific iNKT subsets, in which TCR-dependent activation of IRE1 alpha is associated with downstream activation of p38 MAPK and the stabilization of preformed cytokine mRNAs. Importantly, genetic deletion of IRE1 alpha in iNKT cells reduces cytokine production and protects mice from oxazolone colitis. We therefore propose that an IRE1 alpha-dependent signaling cascade couples constitutive cytokine mRNA expression to the rapid induction of cytokine secretion and effector functions in activated iNKT cells.
Keywords
UNFOLDED PROTEIN RESPONSE, ENDOPLASMIC-RETICULUM, STRESS-RESPONSE, OXAZOLONE COLITIS, NKT CELLS, ACTIVATION, IRE1-ALPHA, TRANSCRIPTION, XBP-1, DIFFERENTIATION

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MLA
Govindarajan, Srinath et al. “Stabilization of Cytokine mRNAs in iNKT Cells Requires the Serine-threonine Kinase IRE1alpha.” NATURE COMMUNICATIONS 9 (2018): n. pag. Print.
APA
Govindarajan, S., Gaublomme, D., Van der Cruyssen, R., Verheugen, E., Van Gassen, S., Saeys, Y., Tavernier, S., et al. (2018). Stabilization of cytokine mRNAs in iNKT cells requires the serine-threonine kinase IRE1alpha. NATURE COMMUNICATIONS, 9.
Chicago author-date
Govindarajan, Srinath, Djoere Gaublomme, Renée Van der Cruyssen, Eveline Verheugen, Sofie Van Gassen, Yvan Saeys, Simon Tavernier, et al. 2018. “Stabilization of Cytokine mRNAs in iNKT Cells Requires the Serine-threonine Kinase IRE1alpha.” Nature Communications 9.
Chicago author-date (all authors)
Govindarajan, Srinath, Djoere Gaublomme, Renée Van der Cruyssen, Eveline Verheugen, Sofie Van Gassen, Yvan Saeys, Simon Tavernier, Takao Iwawaki, Yehudi Bloch, Savvas Savvides, Bart Lambrecht, Sophie Janssens, Dirk Elewaut, and Michael Drennan. 2018. “Stabilization of Cytokine mRNAs in iNKT Cells Requires the Serine-threonine Kinase IRE1alpha.” Nature Communications 9.
Vancouver
1.
Govindarajan S, Gaublomme D, Van der Cruyssen R, Verheugen E, Van Gassen S, Saeys Y, et al. Stabilization of cytokine mRNAs in iNKT cells requires the serine-threonine kinase IRE1alpha. NATURE COMMUNICATIONS. 2018;9.
IEEE
[1]
S. Govindarajan et al., “Stabilization of cytokine mRNAs in iNKT cells requires the serine-threonine kinase IRE1alpha,” NATURE COMMUNICATIONS, vol. 9, 2018.
@article{8601530,
  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 1 alpha (IRE1 alpha), links key cellular processes required for iNKT cell effector functions in specific iNKT subsets, in which TCR-dependent activation of IRE1 alpha is associated with downstream activation of p38 MAPK and the stabilization of preformed cytokine mRNAs. Importantly, genetic deletion of IRE1 alpha in iNKT cells reduces cytokine production and protects mice from oxazolone colitis. We therefore propose that an IRE1 alpha-dependent signaling cascade couples constitutive cytokine mRNA expression to the rapid induction of cytokine secretion and effector functions in activated iNKT cells.},
  articleno    = {5340},
  author       = {Govindarajan, Srinath and Gaublomme, Djoere and Van der Cruyssen, Renée and Verheugen, Eveline and Van Gassen, Sofie and Saeys, Yvan and Tavernier, Simon and Iwawaki, Takao and Bloch, Yehudi and Savvides, Savvas and Lambrecht, Bart and Janssens, Sophie and Elewaut, Dirk and Drennan, Michael},
  issn         = {2041-1723},
  journal      = {NATURE COMMUNICATIONS},
  keywords     = {UNFOLDED PROTEIN RESPONSE,ENDOPLASMIC-RETICULUM,STRESS-RESPONSE,OXAZOLONE COLITIS,NKT CELLS,ACTIVATION,IRE1-ALPHA,TRANSCRIPTION,XBP-1,DIFFERENTIATION},
  language     = {eng},
  pages        = {12},
  title        = {Stabilization of cytokine mRNAs in iNKT cells requires the serine-threonine kinase IRE1alpha},
  url          = {http://dx.doi.org/10.1038/s41467-018-07758-x},
  volume       = {9},
  year         = {2018},
}

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