| First Author | Adrover JM | Year | 2019 |
| Journal | Immunity | Volume | 50 |
| Issue | 2 | Pages | 390-402.e10 |
| PubMed ID | 30709741 | Mgi Jnum | J:282430 |
| Mgi Id | MGI:6380894 | Doi | 10.1016/j.immuni.2019.01.002 |
| Citation | Adrover JM, et al. (2019) A Neutrophil Timer Coordinates Immune Defense and Vascular Protection. Immunity 50(2):390-402.e10 |
| abstractText | Neutrophils eliminate pathogens efficiently but can inflict severe damage to the host if they over-activate within blood vessels. It is unclear how immunity solves the dilemma of mounting an efficient anti-microbial defense while preserving vascular health. Here, we identify a neutrophil-intrinsic program that enabled both. The gene Bmal1 regulated expression of the chemokine CXCL2 to induce chemokine receptor CXCR2-dependent diurnal changes in the transcriptional and migratory properties of circulating neutrophils. These diurnal alterations, referred to as neutrophil aging, were antagonized by CXCR4 (C-X-C chemokine receptor type 4) and regulated the outer topology of neutrophils to favor homeostatic egress from blood vessels at night, resulting in boosted anti-microbial activity in tissues. Mice engineered for constitutive neutrophil aging became resistant to infection, but the persistence of intravascular aged neutrophils predisposed them to thrombo-inflammation and death. Thus, diurnal compartmentalization of neutrophils, driven by an internal timer, coordinates immune defense and vascular protection. |
