2024-03-29T02:22:55Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/2398652022-11-03T10:47:35Zcom_10261_25com_10261_1col_10261_278
Adrover, José M.
Fresno, Carlos del
Crainiciuc, Georgiana
Cuartero, María Isabel
Casanova-Acebes, María
Weiss, L.A.
Huerga Encabo, Héctor
Silvestre-Roig, C.
Rossaint, Jan
Cossío, Itziar
Lechuga-Vieco, Ana V.
García-Prieto, Jaime
Gómez-Parrizas, Mónica
Quintana, Juan A.
Ballesteros, Iván
Martin-Salamanca, Sandra
Aroca-Crevillen, Alejandra
Zhen Chong, Shu
Evrard, Maximilien
Balabanian, Karl
López, Jorge
Bidzhekov, Kiril
Bachelerie, Françoise
Abad-Santos, Francisco
Muñoz-Calleja, Cecilia
Zarbock, Alexander
Soehnlein, Oliver
Weber, C.
Guan Ng, Lai
López-Rodríguez, Cristina
Sancho, David
Moro, María A.
Ibáñez, Borja
Hidalgo, Andrés
2021-05-05T09:10:02Z
2021-05-05T09:10:02Z
2019-02-19
Immunity 50(2): 390-402.e10 (2019)
http://hdl.handle.net/10261/239865
10.1016/j.immuni.2019.01.002
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100000781
http://dx.doi.org/10.13039/501100001659
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100010198
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. Neutrophils display circadian oscillations in numbers and phenotype in the circulation. Adrover and colleagues now identify the molecular regulators of neutrophil aging and show that genetic disruption of this process has major consequences in immune cell trafficking, anti-microbial defense, and vascular health.
closedAccess
Neutrophil
Circadian clock
Inflammation
Infection
Myocardial infarction
Neutrophil aging
Candida albicans
Bmal
1CXCR2
CXCR4
A Neutrophil Timer Coordinates Immune Defense and Vascular Protection
artículo