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He, Wenyan; Holtkamp, Stephan; Hergenhan, Sophia Martina; Kraus, Kerstin; Juan, Alba de; Weber, Jasmin; Bradfield, Paul; Grenier, Julien Martin Pierre; Pelletier, Jeoffrey; Druzd, David; Chen, Chien-Sin; Ince, Louise Madeleine; Bierschenk, Susanne; Pick, Robert; Sperandio, Markus; Aurrand-Lions, Michel; Scheiermann, Christoph (2018): Circadian Expression of Migratory Factors Establishes Lineage-Specific Signatures that Guide the Homing of Leukocyte Subsets to Tissues. In: Immunity, Vol. 49, No. 6: pp. 1175-1190
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Abstract

The number of leukocytes present in circulation varies throughout the day, reflecting bone marrow output and emigration from blood into tissues. Using an organism-wide circadian screening approach, we detected oscillations in pro-migratory factors that were distinct for specific vascular beds and individual leukocyte subsets. This rhythmic molecular signature governed time-of-day-dependent homing behavior of leukocyte subsets to specific organs. Ablation of BMAL1, a transcription factor central to circadian clock function, in endothelial cells or leukocyte subsets demonstrated that rhythmic recruitment is dependent on both microenvironmental and cell-autonomous oscillations. These oscillatory patterns defined leukocyte trafficking in both homeostasis and inflammation and determined detectable tumor burden in blood cancer models. Rhythms in the expression of pro-migratory factors and migration capacities were preserved in human primary leukocytes. The definition of spatial and temporal expression profiles of pro-migratory factors guiding leukocyte migration patterns to organs provides a resource for the further study of the impact of circadian rhythms in immunity.