Chronic Stress Physically Spares but Functionally Impairs Innate-like Invariant T cells

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2021 Apr 14

PMID 33852855

Citations 22

Authors

Patrick T Rudak

Joshua Choi

Katie M Parkins

Kelly L Summers

Dwayne N Jackson

Paula J Foster

Anton I Skaro

Ken Leslie

Vivian C McAlister

Vijay K Kuchroo

Wataru Inoue

Olivier Lantz

S M Mansour Haeryfar

Affiliations

Soon will be listed here.

Abstract

The deleterious effects of psychological stress on mainstream T lymphocytes are well documented. However, how stress impacts innate-like T cells is unclear. We report that long-term stress surprisingly abrogates both T helper 1 (T1)- and T2-type responses orchestrated by invariant natural killer T (iNKT) cells. This is not due to iNKT cell death because these cells are unusually refractory to stress-inflicted apoptosis. Activated iNKT cells in stressed mice exhibit a "split" inflammatory signature and trigger sudden serum interleukin-10 (IL-10), IL-23, and IL-27 spikes. iNKT cell dysregulation is mediated by cell-autonomous glucocorticoid receptor signaling and corrected upon habituation to predictable stressors. Importantly, under stress, iNKT cells fail to potentiate cytotoxicity against lymphoma or to reduce the burden of metastatic melanoma. Finally, stress physically spares mouse mucosa-associated invariant T (MAIT) cells but hinders their T1-/T2-type responses. The above findings are corroborated in human peripheral blood and hepatic iNKT/MAIT cell cultures. Our work uncovers a mechanism of stress-induced immunosuppression.

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