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Neutrophil infiltration regulates clock-gene expression to organize daily hepatic metabolism

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dc.contributor.authorCrespo, Maria
dc.contributor.authorGonzalez-Teran, Barbara
dc.contributor.authorNikolic, Ivana
dc.contributor.authorMora, Alfonso
dc.contributor.authorFolgueira, Cintia
dc.contributor.authorLeiva-Vega, Luis
dc.contributor.authorPintor-Chocano, Aranzazu
dc.contributor.authorMacarena, Fernández-Chacón
dc.contributor.authorIrene, Ruiz-Garrido
dc.contributor.authorCicuéndez, Beatriz
dc.contributor.authorTomas-Loba, Antonia
dc.contributor.authorA-Gonzalez, Noelia
dc.contributor.authorCabllero-Molano, Ainoa
dc.contributor.authorBeiroa, Daniel
dc.contributor.authorHernández-Cosido, Lourdes
dc.contributor.authorTorres, Jorge L
dc.contributor.authorKennedy, Norman J
dc.contributor.authorDavis, Roger J
dc.contributor.authorBenedito, Rui
dc.contributor.authorMarcos, Miguel
dc.contributor.authorNogueiras, Ruben
dc.contributor.authorHidalgo, Andres
dc.contributor.authorMatesanz, Nuria
dc.contributor.authorLeiva, Magdalena
dc.contributor.authorSabio, Guadalupe
dc.contributor.departmentFisiología
dc.date.accessioned2024-02-07T08:12:10Z
dc.date.available2024-02-07T08:12:10Z
dc.date.issued2020-12-08
dc.description©<2020>. This manuscript version is made available under the CC-BY license http://creativecommons.org/licenses/by/4.0/ This document is the published version of a Published Work that appeared in final form in [eLife]. To access the final edited and published work see [https://doi.org/10.7554/eLife.59258]
dc.description.abstractLiver metabolism follows diurnal fluctuations through the modulation of molecular clock genes. Disruption of this molecular clock can result in metabolic disease but its potential regulation by immune cells remains unexplored. Here, we demonstrated that in steady state, neutrophils infiltrated the mouse liver following a circadian pattern and regulated hepatocyte clock- genes by neutrophil elastase (NE) secretion. NE signals through c-Jun NH2-terminal kinase (JNK) inhibiting fibroblast growth factor 21 (FGF21) and activating Bmal1 expression in the hepatocyte. Interestingly, mice with neutropenia, defective neutrophil infiltration or lacking elastase were protected against steatosis correlating with lower JNK activation, reduced Bmal1 and increased FGF21 expression, together with decreased lipogenesis in the liver. Lastly, using a cohort of human samples we found a direct correlation between JNK activation, NE levels and Bmal1 expression in the liver. This study demonstrates that neutrophils contribute to the maintenance of daily hepatic homeostasis through the regulation of the NE/JNK/Bmal1 axis.
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dc.identifier.citationeLife 2020;9:e59258, 2020
dc.identifier.doihttps://doi.org/10.7554/eLife.59258
dc.identifier.issnElectrónico: 2050-084X
dc.identifier.urihttp://hdl.handle.net/10201/138774
dc.languageenges
dc.publishereLife Sciences Publicationses
dc.relationEuropean Commission (ERC260464) Ministerio de Economía y Competitividad (SAF2016-79126-R) Ministerio de Economía y Competitividad (SAF2015-74112-JIN) Fundación Científica Asociación Española Contra el Cáncer (INVES20026LEIV PROYE19047SABI) Ministerio de Ciencia e Innovación (PID2019-104399RB-I00) FPI Severo Ochoa- CNIC (SVP‐2013‐067639) Ministerio de Economía y Competitividad (BES-2017-079711) Juan de la Cierva (JCI-2011-11623) Sara Borrell (CD19/00078) National Institutes of Health (DK R01 DK107220) Ministerio de Economía y Competitividad (SAF2014-61233-JIN) Fundación BBVA (IN[17]_BBM_BAS_0066) Ministerio de Economía y Competitividad (EUIN2017-85875) Comunidad de Madrid (S2010/BMD-2326) Comunidad de Madrid (B2017/BMD-3733) Instituto de Salud Carlos III (PI16/01548) Junta de Castilla y León (GRS1362/A/16) Junta de Castilla y León (INT/M/17/17) Junta de Castilla y León (GRS 1356/A/16) Junta de Castilla y León (GRS 1587/A/17) European Foundation for the Study of Diabetes (ESFD/Lilly Programme) European Foundation for the Study of Diabetes (EFSD/Lilly Grant 2017 and 2019) CNIC IPP FP7 Marie Curie Programme (PCOFUND-2012-600396) European Foundation for the Study of Diabetes (EFSD Rising Star award 2019) Juan de la Cierva (JDC-2018-Incorporación MIN/JDC1802)es
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.otherCDU::5 - Ciencias puras y naturales::57 - Ciencias biológicas en general:577 - 577 Bioquímica. Biología molecular. Biofísica
dc.titleNeutrophil infiltration regulates clock-gene expression to organize daily hepatic metabolismes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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