Homing of metastatic cells to lung is regulated by neutrophils. (A) Disrupted diurnal infiltration of Bmal1^ΔN neutrophils into lungs. Experimental design. (B) Relative number of partner-derived neutrophils in the lungs of partner mice at AM or PM (ZT4 and 16, respectively), determined by flow cytometry; n = 4 (for Bmal1^ΔN) to 20 (for WT) mice. ND, not determined for neutrophil-depleted (1A8 antibody) mice. (C) Relative homing of B16F1Luc cells to the lungs of control, neutrophil-depleted mice and Bmal1^ΔN mice, as determined by flow cytometry 24 h after injection; n = 3–5 mice (control and depleted) or 9 (Bmal1^ΔN) per time and experiment from at least two independent experiments. Values are normalized to AM. Values show mean ± SEM. *, P < 0.05; n.s., not significant, comparing AM versus AM or PM versus PM values, as determined by Student’s two-tailed unpaired t test analysis. (D) Schematic of neutrophil dynamics during homeostasis and physiological roles in intestine and lungs. Neutrophils released from the BM into blood infiltrate multiple tissues with distinct circadian dynamics (boxes next to tissue names). Most tissues display rhythms in anti-phase with blood, while infiltration in liver, WAT, and intestine are arrhythmic. Illustration of remote control of hematopoietic niches through modulation of Il23 transcription within intestinal ILF (bottom left box). In the lung, neutrophils regulated diurnal transcription (bottom right box), thereby affecting the susceptibility to metastatic invasion by B16F1 melanoma cells (right; see also Video 10).