@article{db1c0e1e67df4c49b62c7452e954b9d2,
title = "Programmed 'disarming' of the neutrophil proteome reduces the magnitude of inflammation",
abstract = "The antimicrobial functions of neutrophils are facilitated by a defensive armamentarium of proteins stored in granules, and by the formation of neutrophil extracellular traps (NETs). However, the toxic nature of these structures poses a threat to highly vascularized tissues, such as the lungs. Here, we identified a cell-intrinsic program that modified the neutrophil proteome in the circulation and caused the progressive loss of granule content and reduction of the NET-forming capacity. This program was driven by the receptor CXCR2 and by regulators of circadian cycles. As a consequence, lungs were protected from inflammatory injury at times of day or in mouse mutants in which granule content was low. Changes in the proteome, granule content and NET formation also occurred in human neutrophils, and correlated with the incidence and severity of respiratory distress in pneumonia patients. Our findings unveil a 'disarming' strategy of neutrophils that depletes protein stores to reduce the magnitude of inflammation.Hidalgo and colleagues describe a cell-intrinsic program that induces changes in the proteome, granule content and NET-forming capacity of neutrophils and is driven by the chemokine receptor CXCR2 and regulators of the circadian clock.",
keywords = "CIRCADIAN VARIATION, SECRETORY VESICLES, SERINE PROTEASES, GRANULE SUBSETS, MARROW, PATHOGENESIS, PLATELETS, ELASTASE, EFFECTOR, TRAPS",
author = "Adrover, {Jose M.} and Alejandra Aroca-Crevillen and Georgiana Crainiciuc and Fernando Ostos and Yeny Rojas-Vega and Andrea Rubio-Ponce and Catia Cilloniz and Elena Bonzon-Kulichenko and Enrique Calvo and Daniel Rico and Moro, {Maria A.} and Christian Weber and Ignacio Lizasoain and Antoni Torres and Jesus Ruiz-Cabello and Jesus Vazquez and Andres Hidalgo",
note = "Funding Information: We thank members of the Comparative Medicine Unit and Advanced Microscopy Unit at CNIC. This study was supported by Intramural grants from the Severo Ochoa program (IGP-SO), a grant from Fundaci{\'o} La Marat{\'o} de TV3 (120/C/2015-20153032), grant SAF2015-65607-R from Ministerio de Ciencia, Investigacion y Universidades (MCIU) with cofunding from Fondo Europeo de Desarrollo Regional, grant RTI2018-095497-B-I00 from MCIU and HR17_00527 from Fundaci{\'o}n La Caixa (to A.H.), and fellowship BES-2013-065550 from MCIU (to J.M.A.), fellowship from La Caixa Foundation (ID 100010434, code LCF/BQ/DR19/11740022, to A.A.-C.) and fellowship Health-PERIS 2016–2020 (to C.C.) Funds were also obtained from Instituto de Salud Carlos III (FIS PI17/01601, to I.L.) and SAF2015-68632-R from MCIU (to M.A.M.); Wellcome Trust Seed Award in Science (206103/Z/17/Z, to D.R.), SFB1123-A1/A10 from Deutsche Forschungsgemeinschaft and ERC-AdG 692511 (to C.W.); SAF2017-84494-C2-R and Programa Red Guipuzcoana de Ciencia, Tecnolog{\'i}a e Informaci{\'o}n 2018-CIEN-000058-01 (to J.R.-C.). Work at CIC biomaGUNE was performed under the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency (MDM-2017-0720). C.W. is a van de Laar professor of atherosclerosis. The CNIC is supported by the MCIU and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (MEIC award SEV-2015-0505). Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2020",
month = feb,
doi = "10.1038/s41590-019-0571-2",
language = "English",
volume = "21",
pages = "135--144",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "2",
}