Chronic stress physically spares but functionally impairs innate-like invariant T cells

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

Cell Reports (Apr 2021)

Chronic stress physically spares but functionally impairs innate-like invariant T cells

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

Patrick T. Rudak: Department of Microbiology and Immunology, Western University, London, ON N6A 5C1, Canada
Joshua Choi: Department of Microbiology and Immunology, Western University, London, ON N6A 5C1, Canada
Katie M. Parkins: Department of Medical Biophysics, Western University, London, ON N6A 5C1, Canada; Robarts Research Institute, Western University, London, ON N6A 5B7, Canada
Kelly L. Summers: Department of Microbiology and Immunology, Western University, London, ON N6A 5C1, Canada
Dwayne N. Jackson: Department of Medical Biophysics, Western University, London, ON N6A 5C1, Canada
Paula J. Foster: Department of Medical Biophysics, Western University, London, ON N6A 5C1, Canada; Robarts Research Institute, Western University, London, ON N6A 5B7, Canada
Anton I. Skaro: Department of Surgery, Division of General Surgery, Western University, London, ON N6A 4V2, Canada
Ken Leslie: Department of Surgery, Division of General Surgery, Western University, London, ON N6A 4V2, Canada
Vivian C. McAlister: Department of Surgery, Division of General Surgery, Western University, London, ON N6A 4V2, Canada
Vijay K. Kuchroo: Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA 02115, USA
Wataru Inoue: Robarts Research Institute, Western University, London, ON N6A 5B7, Canada; Department of Physiology and Pharmacology, Western University, London, ON N6A 5C1, Canada
Olivier Lantz: Laboratoire d’Immunologie and INSERM U932, PSL University, Institut Curie, 75248 Paris Cedex 5, France
S.M. Mansour Haeryfar: Department of Microbiology and Immunology, Western University, London, ON N6A 5C1, Canada; Department of Surgery, Division of General Surgery, Western University, London, ON N6A 4V2, Canada; Department of Medicine, Division of Clinical Immunology and Allergy, Western University, London, ON N6A 5A5, Canada; Corresponding author

Journal volume & issue: Vol. 35, no. 2
p. 108979

Abstract

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Summary: 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 (TH1)- and TH2-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 TH1-/TH2-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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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