Department of Microbiology and Immunology, Western University, London, ON N6A 5C1, Canada.
Department of Medical Biophysics, Western University, London, ON N6A 5C1, Canada; Robarts Research Institute, Western University, London, ON N6A 5B7, Canada.
Cell Rep. 2021 Apr 13;35(2):108979. doi: 10.1016/j.celrep.2021.108979.
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.
心理压力对主流 T 淋巴细胞的有害影响已有充分的文献记载。然而，压力如何影响先天样 T 细胞尚不清楚。我们报告称，长期压力出人意料地破坏了不变自然杀伤 T(iNKT)细胞协调的 T 辅助 1(T1)和 T2 型反应。这不是由于 iNKT 细胞死亡，因为这些细胞对压力诱导的细胞凋亡异常具有抗性。应激小鼠中激活的 iNKT 细胞表现出“分裂”炎症特征，并引发血清白细胞介素-10(IL-10)、IL-23 和 IL-27 的突然飙升。iNKT 细胞的失调是通过细胞自主糖皮质激素受体信号转导介导的，并在适应可预测的应激源时得到纠正。重要的是，在应激下，iNKT 细胞不能增强对淋巴瘤的细胞毒性或减少转移性黑色素瘤的负担。最后，压力使小鼠黏膜相关不变 T(MAIT)细胞免受影响，但阻碍了它们的 T1/T2 型反应。上述发现得到了人类外周血和肝 iNKT/MAIT 细胞培养的证实。我们的工作揭示了一种应激诱导免疫抑制的机制。
