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oai:repisalud.isciii.es:20.500.12105/78642024-09-27T09:41:02Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Adrover, Jose M author del Fresno, Carlos author Crainiciuc, Georgiana author Cuartero, Maria Isabel author Casanova-Acebes, Maria author Weiss, Linnea A author Huerga-Encabo, Hector author Silvestre-Roig, Carlos author Rossaint, Jan author Cossio, Itziar author Lechuga-Vieco, Ana V. author Garcia-Prieto, Jaime author Gomez-Parrizas, Monica author Quintana, Juan A. author Ballesteros, Ivan author Martin-Salamanca, Sandra author Aroca-Crevillen, Alejandra author Chong, Shu Zhen author Evrard, Maximilien author Balabanian, Karl author López, Jorge author Bidzhekov, Kiril author Bachelerie, Françoise author Abad-Santos, Francisco author Muñoz-Calleja, Cecilia author Zarbock, Alexander author Soehnlein, Oliver author Weber, Christian author Ng, Lai Guan author Lopez-Rodriguez, Cristina author Sancho, David author Moro, Maria Angeles author Ibáñez, Borja author Hidalgo, Andres author 2019-02 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. Immunity. 2019; 50(2):390-402 10.1016/j.immuni.2019.01.002 1097-4180 1074-7613 Immunity 30709741 http://hdl.handle.net/20.500.12105/7864 Bmal1 CXCR2 CXCR4 Candida albicans Neutrophil Circadian clock Infection Inflammation Myocardial infarction Neutrophil aging A Neutrophil Timer Coordinates Immune Defense and Vascular Protection