Circadian Features of Neutrophil Biology

Abstract

Rhythms in immunity manifest in multiple ways, but perhaps most prominently by the recurrent onset of inflammation at specific times of day. These patterns are of importance to understand human disease and are caused, in many instances, by the action of neutrophils, a myeloid leukocyte with striking circadian features. The neutrophil's short life, marked diurnal variations in number, and changes in phenotype while in the circulation, help explain the temporal features of inflammatory disease but also uncover core features of neutrophil physiology. Here, we summarize well-established concepts and introduce recent discoveries in the biology of these cells as they relate to circadian rhythms. We highlight that although the circadian features of neutrophils are better known and relevant to understand disease, they may also influence important aspects of organ function even in the steady-state. Finally, we discuss the possibility of targeting these temporal features of neutrophils for therapeutic benefit.

The Secretive Life of Neutrophils Revealed by Intravital Microscopy

“…This is also the case for humans, but with the clock inverted (Adrover et al, 2020). The impact of circadian rhythms on neutrophil mobilization, clearance, and inflammation has been more extensively reviewed here (Scheiermann et al, 2013;Hidalgo et al, 2019;Adrover et al, 2020;Aroca-Crevillen et al, 2020).…”

The complexity of neutrophils in health and disease: Focus on cancer

“…Neutrophils have a short lifespan and their presence in the circulation requires a continuous production in the bone marrow (BM), which is mainly regulated by the production of granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) [ 1 , [24] , [25] , [26] ]. In humans, up to 2 × 10 11 neutrophils are produced daily during the process of granulopoiesis in the BM and released in the bloodstream [ 1 ].…”

“…During their maturation, expression of CXCR4 on the surface of neutrophils is downregulated, while the expression of CXCR2 is increased, leading to their release in the blood via the interaction with CXC chemokines (e.g. CXCL1, CXCL2) present in the circulation [ 15 , 24 , 49 , 50 ]. Circulating aged neutrophils upregulate the expression of CXCR4 in order to migrate into the BM where they are eliminated by macrophages [ 51 ].…”

Population pharmacodynamic modeling of intramuscular and oral dexamethasone and betamethasone effects on six biomarkers with circadian complexities in Indian women

“…The circadian rhythm in baseline neutrophils is attributed to the cytokine CXCL12 that controls the release of neutrophils from the bone marrow. CXCL12 undergoes circadian changes in expression stimulated by the sympathetic nervous system [ 14 ]. The light–dark cycle regulates glucose metabolism via the central clock.…”