The circadian clock sets a spatial‐temporal window for recent thymic emigrants
The circadian clock sets a spatial‐temporal window for recent thymic emigrants
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生物钟为最近的胸腺移民设置了一个空间和时间窗口
DOI：
10.1111/imcb.12582
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Rong Jin
中科院分区：
文献类型：
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作者：
Mili Minaduola;Abudureyimujiang Aili;Yuhui Bao;Zhi Peng;Qing Ge;Rong Jin
昼夜计时系统调节外周淋巴器官中淋巴细胞的多种功能。目前尚不清楚胸腺中T细胞的发育和胸腺中T细胞的流出是否受生物钟的影响。在这里，我们使用流式细胞术来检测从Zeitgebertime(ZT)1到ZT21的胸腺细胞总数和百分比以及胸腺细胞的不同亚群。CD4和CD8单阳性(SP)胸腺细胞，特别是胸腺血管周间隙中成熟的具有迁出能力的CD4SP4胸腺细胞亚群和PE+CD4SP胸腺细胞，表现出强烈的昼夜振荡。SP胸腺细胞上S1PR1和CCR2的昼夜表达以及外周血和胸腺之间形成的节律性S1P和CCL2梯度可能促进了SP胸腺细胞的昼夜节律外流。转换日光周期扰乱了S1PR1和CCR2表达的节律以及随后胸腺细胞的输出。我们进一步证明了核心时钟分子BMAL1具有KLF2、S1PR1和Sphk2启动子的节律性结合。我们一起阐明了成熟胸腺细胞外流的昼夜动态特征，这与T细胞归巢到淋巴结的日变化相一致。核心节律分子BMAL1可能通过对迁移相关分子的转录调控促进胸腺细胞迁移。
The diurnal timing system regulates multiple functions of lymphocytes in peripheral lymphoid organs. Whether T-cell development in the thymus and T-cell egress from the thymus are affected by the circadian clock is not clear. Herein, we used flow cytometry to examine the cell number and percentage of total thymocytes and various thymocyte subsets from Zeitgebertime (ZT) 1 to ZT21. CD4 and CD8 single-positive (SP) thymocytes, in particular, the mature CD4 SP4 thymocyte subset with emigration capability and PE+ CD4 SP thymocytes in the perivascular space of the thymus, exhibited robust circadian oscillations. The diurnal expression of S1PR1 and CCR2 on SP thymocytes and the rhythmic S1P and CCL2 gradient formed between peripheral blood and thymus likely promoted SP thymocyte egress in a circadian pattern. Switching the daylight cycle disturbed the rhythm of S1PR1 and CCR2 expression and subsequent thymocyte output. We further demonstrated that the core clock molecule BMAL1 had rhythmic binding of the promoters of Klf2, S1pr1 and Sphk2. Together, we elucidated the circadian dynamic characteristics of mature thymocyte egress, which coordinated with the diurnal changes in T-cell homing to the lymph nodes. The core rhythmic molecule BMAL1 likely promoted thymocyte emigration through transcriptional regulation of emigration-related molecules.