1. Chronic stress physically spares but functionally impairs innate-like invariant T cells
- Author
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K. L. Summers, Ken Leslie, Anton I. Skaro, S. M. Mansour Haeryfar, Wataru Inoue, Vijay K. Kuchroo, Paula J. Foster, Joshua Choi, Olivier Lantz, Patrick T. Rudak, Vivian C. McAlister, Katie M. Parkins, and Dwayne N. Jackson
- Subjects
Cytotoxicity, Immunologic ,Male ,0301 basic medicine ,Lymphoma ,medicine.medical_treatment ,Cell ,Interleukin-23 ,Mice ,0302 clinical medicine ,Conditional gene knockout ,Chronic stress ,Neoplasm Metastasis ,050207 economics ,Biology (General) ,Cytotoxicity ,Th1-Th2 Balance ,innate immunity ,Mice, Inbred BALB C ,050208 finance ,Liver Neoplasms ,05 social sciences ,T-Lymphocytes, Helper-Inducer ,habituation ,Interleukin-10 ,Cell biology ,3. Good health ,Gene Expression Regulation, Neoplastic ,Cytokine ,medicine.anatomical_structure ,cytotoxicity ,Female ,Signal Transduction ,Programmed cell death ,QH301-705.5 ,MAIT cells ,Mice, Transgenic ,Biology ,Article ,Mucosal-Associated Invariant T Cells ,General Biochemistry, Genetics and Molecular Biology ,Immobilization ,03 medical and health sciences ,Immunity ,Cell Line, Tumor ,0502 economics and business ,medicine ,Animals ,Humans ,Oxidopamine ,psychological stress ,iNKT cells ,Innate immune system ,Interleukins ,medicine.disease ,Immunity, Innate ,030104 developmental biology ,Cell culture ,Apoptosis ,Chronic Disease ,Immunology ,Natural Killer T-Cells ,Corticosterone ,Stress, Psychological ,030217 neurology & neurosurgery - Abstract
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., In brief Invariant T cells are emergency responders to infection and cancer. Rudak et al. report that psychological stress unusually spares these innate-like T lymphocytes but alters or impairs their cytokine production and cytotoxic and/or antimetastatic capacities through a cell-autonomous, glucocorticoid receptor-dependent mechanism. This may explain certain aspects of stress-induced immunosuppression., Graphical Abstract
- Published
- 2021