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

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? (IRE1?), links key cellular processes required for iNKT cell effector functions in specific iNKT subsets, in which TCR-dependent activation of IRE1? is associated with downstream activation of p38 MAPK and the stabilization of preformed cytokine mRNAs. Importantly, genetic deletion of IRE1? in iNKT cells reduces cytokine production and protects mice from oxazolone colitis. We therefore propose that an IRE1?-dependent signaling cascade couples constitutive cytokine mRNA expression to the rapid induction of cytokine secretion and effector functions in activated iNKT cells.

SUBMITTER: Govindarajan S 

PROVIDER: S-EPMC6297233 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature