Abstract
The circulating of leukocytes in the vasculature to reach various organs is a crucial step that allows them to perform their function. With a sequence of interaction with the endothelial cells, the leukocytes emigrate from the circulation either by firm attachment to vascular beds or by trafficking into the tissues. Recent findings reveal that the leukocyte recruitment shows time as well as tissue specificity depending on the cell type and homing location. This spatiotemporal distribution of leukocyte subsets is driven by the circadian expression of pro-migratory molecules expressed on the leukocytes and the endothelium. Both the systemic circadian signals and the cell's intrinsic molecule clock contribute to the oscillatory expression of pro-migratory molecules. The rhythmic recruitment of leukocytes plays an important role in the time-dependency of immune responses. It also helps to update blood components and maintain the tissue circadian microenvironment. In this review, we discuss the current knowledge about the mechanisms of the circadian system regulating the leukocyte rhythmic migration, the recruitment pattern of leukocyte subsets into different tissue/organs, and the time-dependent effects behind this process.
Highlights
Blood leukocyte numbers display circadian rhythms in various mammalian species, like rodents [1] and human [2], with a consistent trend, showing a peak in the resting phase and a trough in the activity phase for most of the leukocyte subsets [3]
It has been proved that the major leukocyte subsets, including neutrophils, inflammatory monocytes, non-inflammatory monocytes, CD4 T cells, CD8 T cells, NK cells, and eosinophils, emigrate from the mouse’s blood stream and recruit into distinct tissue/organs in a rhythmic manner with the highest homing occurring at the rest-activity transition phase [3]
The optimal efficacy of those migration blockers is acquired at the rest-activity transition time point when ICAM-1, VCAM-1, CXCR4, and CD49d reach their peak expression levels [3], indicating that the circadian recruitment of leukocytes is dependent on the oscillatory expression of pro-migratory molecules
Summary
Specialty section: This article was submitted to Molecular Innate Immunity, a section of the journal. A Tissue-Specific Rhythmic Recruitment Pattern of Leukocyte Subsets. Recent findings reveal that the leukocyte recruitment shows time as well as tissue specificity depending on the cell type and homing location. This spatiotemporal distribution of leukocyte subsets is driven by the circadian expression of pro-migratory molecules expressed on the leukocytes and the endothelium. The rhythmic recruitment of leukocytes plays an important role in the time-dependency of immune responses. We discuss the current knowledge about the mechanisms of the circadian system regulating the leukocyte rhythmic migration, the recruitment pattern of leukocyte subsets into different tissue/organs, and the time-dependent effects behind this process
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