Laboratory of Immune Regulation, Department of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan; Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Laboratory of Immune Regulation, Department of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
Immunity. 2018 Feb 20;48(2):286-298.e6. doi: 10.1016/j.immuni.2018.01.004. Epub 2018 Jan 27.
Glucocorticoids are steroid hormones with strong anti-inflammatory and immunosuppressive effects that are produced in a diurnal fashion. Although glucocorticoids have the potential to induce interleukin-7 receptor (IL-7R) expression in T cells, whether they control T cell homeostasis and responses at physiological concentrations remains unclear. We found that glucocorticoid receptor signaling induces IL-7R expression in mouse T cells by binding to an enhancer of the IL-7Rα locus, with a peak at midnight and a trough at midday. This diurnal induction of IL-7R supported the survival of T cells and their redistribution between lymph nodes, spleen, and blood by controlling expression of the chemokine receptor CXCR4. In mice, T cell accumulation in the spleen at night enhanced immune responses against soluble antigens and systemic bacterial infection. Our results reveal the immunoenhancing role of glucocorticoids in adaptive immunity and provide insight into how immune function is regulated by the diurnal rhythm.
糖皮质激素是具有强大抗炎和免疫抑制作用的甾体激素，呈昼夜节律分泌。尽管糖皮质激素有可能在 T 细胞中诱导白细胞介素-7 受体（IL-7R）的表达，但它们在生理浓度下是否控制 T 细胞的稳态和反应仍不清楚。我们发现糖皮质激素受体信号通过与 IL-7Rα 基因座的增强子结合，在午夜达到峰值，在中午达到低谷，从而诱导小鼠 T 细胞中 IL-7R 的表达。这种昼夜诱导的 IL-7R 通过控制趋化因子受体 CXCR4 的表达，支持 T 细胞的存活及其在淋巴结、脾脏和血液之间的重新分布。在小鼠中，夜间脾脏中 T 细胞的积累增强了对可溶性抗原和全身细菌感染的免疫反应。我们的研究结果揭示了糖皮质激素在适应性免疫中的免疫增强作用，并深入了解了昼夜节律如何调节免疫功能。
