Time-restricted feeding in rest phase alters IgE/mast cell-mediated allergic reaction in mice
Time-restricted feeding in rest phase alters IgE/mast cell-mediated allergic reaction in mice
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休息阶段限时喂养改变小鼠 IgE/肥大细胞介导的过敏反应
DOI：
10.1016/j.alit.2019.09.004
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发表时间：
2020
影响因子：
6.8
通讯作者：
Atsuhito Nakao
中科院分区：
文献类型：
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作者：
Yuki Nakamura;Kayoko Ishimaru;Atsuhito Nakao
生物钟由涉及多个“时钟基因”的细胞自主转录-翻译反馈环组成，通过以循环方式控制大部分基因来调节细胞活动的时间。1在肥大细胞中，时钟基因PER2表达呈~24小时振荡，负向调节高亲和力ε受体(Fc-IgE RI)的表达，从而导致小鼠肥大细胞活化的昼夜变化。2相应地，小鼠被动皮肤过敏反应(PCA)的程度在肥大细胞PER2水平分别降低和升高的“静止期”(夜间小鼠的明/暗周期的光期)和“活跃期”(暗期)分别出现峰值和最低点。2，3外周细胞的昼夜节律时钟活动受摄食时间的影响很大。特别是，将摄食时间从活动期切换到静止期(静止期的限时摄食[TRF])会导致生物钟活动和外周细胞中时钟控制的基因表达发生12小时的偏移。4例如，只在夜间或临时喂食会导致循环肝脏基因表达的相角相似，而白天喂食几乎完全颠倒了这一相角。然而，TRF对肥大细胞时钟和功能的影响尚不清楚。在这项研究中，我们研究了静止期的TRF是否可以改变肥大细胞的时钟活性(例如，PER2的表达)，从而改变FcεRI的表达动力学，改变Ig E/Mast细胞介导的变态反应的时间分布。6将6周龄雄性C57BL/6小鼠、肥大细胞缺陷WBB6F1-W/WV小鼠(日本东京)和Per2Luciferase(Per2Luc)敲入小鼠(背景为C57BL/6背景)置于12h光照/12h黑暗条件下(光照/黑暗[L/D]12：12周期；上午6：00开启光，Zeitgeber时间[ZT]0，下午6：00，ZT12关闭)下随意进食2周。TRF实验进行了20天(1e20天)。骨髓来源的肥大细胞(BMMC)的产生如前所述。2所有动物实验均经山梨大学机构评审委员会批准。有关更多信息，请参阅本文中的补充方法部分。
The circadian clock, which consists of a cell-autonomous transcriptionetranslation feedback loop involving several “clock genes,” regulates the timing of cellular activities by controlling a large proportion of genes in a cyclic manner. 1 In mast cells, the clock gene Period2 (Per2), the expression of which exhibits a~ 24-h oscillation, negatively regulates expression of the high-affinity IgE receptor (FcεRI), thereby contributing to the dayenight variation in IgE-mediated mast cell activation in mice. 2 Accordingly, the extent of passive cutaneous anaphylactic (PCA) reaction, a classical model of IgE/mast cellemediated allergic reaction, in mice exhibits a peak during the “rest phase”(light period of the light/dark cycle in nocturnal mice) and a nadir during the “active phase”(dark period), when PER2 levels in mast cells decrease and increase, respectively. 2, 3Circadian clock activity in peripheral cells is strongly influenced by the time of day at which feeding occurs. In particular, switching feeding time from active phase to rest phase in mice (time-restricted feeding [TRF] in rest phase) leads to a 12-h shift in circadian clock activity and clock-controlled gene expression in peripheral cells. 4 For example, feeding exclusively during the night or ad libitum results in a similar phase angle of cyclic liver gene expression, whereas feeding during the day almost entirely inverts the phase. 5 However, the effects of TRF on the mast cell clock and function remain unknown. In this study, we investigated whether TRF in rest phase could shift mast cell clock activity (eg, PER2 expression) and thus change the kinetics of FcεRI expression and alter temporal profiles of IgE/mast cellemediated allergic reaction. Male 6-week-old C57BL/6 mice, mast celledeficient WBB6F1-W/Wv mice (Japan SLC, Tokyo, Japan), and Per2Luciferase (Per2Luc) knock-in mice (C57BL/6 background), which express PER2 as a luciferase fusion protein, 6 were housed under 12-h light/12-h dark conditions (light/dark [L/D] 12: 12 cycles; the light was turned on at 6: 00 AM, Zeitgeber time [ZT] 0, and turned off at 6: 00 PM, ZT12) with ad libitum access to food for 2 weeks before the TRF experiments. The TRF experiments were carried out for 20 days (Day 1e20). Bone marrowederived mast cells (BMMCs) were generated as previously described. 2 All animal experiments were approved by the Institutional Review Board of the University of Yamanashi. For more information, see the Supplementary Methods section in this article.