Glucocorticoids Drive Diurnal Oscillations in T Cell Distribution and Responses by Inducing Interleukin-7 Receptor and CXCR4
Glucocorticoids Drive Diurnal Oscillations in T Cell Distribution and Responses by Inducing Interleukin-7 Receptor and CXCR4
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DOI：
10.1016/j.immuni.2018.01.004
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发表时间：
2018-02-20
期刊：
影响因子：
32.4
通讯作者：
Ikuta, Koichi
中科院分区：
文献类型：
--
作者：
Shimba, Akihiro;Cui, Guangwei;Ikuta, Koichi
糖皮质激素是具有强烈抗炎和免疫抑制作用的类固醇激素，以昼夜方式产生。虽然糖皮质激素具有诱导T细胞中白细胞介素-7受体（IL-7 R）表达的潜力，但它们是否在生理浓度下控制T细胞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-7 R α位点的增强子结合诱导小鼠T细胞中的IL-7 R表达，峰值在午夜，谷值在中午。IL-7 R的这种昼夜诱导通过控制趋化因子受体CXCR 4的表达来支持T细胞的存活及其在淋巴结、脾和血液之间的再分布。在小鼠中，夜间脾脏中的T细胞积累增强了针对可溶性抗原和全身性细菌感染的免疫应答。我们的结果揭示了糖皮质激素在获得性免疫中的免疫增强作用，并提供了有关免疫功能如何受昼夜节律调节的见解。
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 inter-leukin-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-7R alpha 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.