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, 3

Circadian 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.