Stress related responses regulate immune function

The immune system is composed of a wide range of different immune cells each with dedicated functions. Natural killer T cells form a specialized immune cell that protects against a variety of diseases such as cancer, autoimmunity, metabolic disease or certain infections such as Lyme disease. This is because of their ability to make very rapidly large amounts of cytokines, which act as major communicators between different cell types.

Why invariant natural killer T (iNKT) cells are able to make these molecules so abundantly was unclear. The researchers report in Nature Communications that a stress related pathway inside the endoplasmic reticulum is instrumental in controlling the function of natural killer T cells.

The authors 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.

This seems to deviate from other immune cells which underscores the selectivity of this mechanism to this particular cell type. The senior author said: "The identification of this stress related response opens new avenues. We believe that the modulation of this response could lead to novel strategies to control diseases mediated by natural killer T cells."

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