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dc.contributor.authorCrespo, Maria
dc.contributor.authorKennedy, Norman J.
dc.contributor.authorDavis, Roger J.
dc.contributor.authorMatesanz, Nuria
dc.contributor.authorLeiva, Magdalena
dc.contributor.authorSabio, Guadalupe
dc.date2022-08-11T08:08:26.000
dc.date.accessioned2022-08-23T15:55:04Z
dc.date.available2022-08-23T15:55:04Z
dc.date.issued2020-12-08
dc.date.submitted2021-01-27
dc.identifier.citation<p>Crespo M, Gonzalez-Teran B, Nikolic I, Mora A, Folgueira C, Rodríguez E, Leiva-Vega L, Pintor-Chocano A, Fernández-Chacón M, Ruiz-Garrido I, Cicuéndez B, Tomás-Loba A, A-Gonzalez N, Caballero-Molano A, Beiroa D, Hernández-Cosido L, Torres JL, Kennedy NJ, Davis RJ, Benedito R, Marcos M, Nogueiras R, Hidalgo A, Matesanz N, Leiva M, Sabio G. Neutrophil infiltration regulates clock-gene expression to organize daily hepatic metabolism. Elife. 2020 Dec 8;9:e59258. doi: 10.7554/eLife.59258. PMID: 33287957; PMCID: PMC7723411. <a href="https://doi.org/10.7554/eLife.59258">Link to article on publisher's site</a></p>
dc.identifier.issn2050-084X (Linking)
dc.identifier.doi10.7554/eLife.59258
dc.identifier.pmid33287957
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29672
dc.description<p>Full author list omitted for brevity. For the full list of authors, see article.</p>
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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=33287957&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright © 2020, Crespo et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectJNK
dc.subjectcell biology
dc.subjectcircadian rhythm
dc.subjectimmunology
dc.subjectinflammation
dc.subjectmouse
dc.subjectneutrophil elastase
dc.subjectsteatosis
dc.subjectliver metabolism
dc.subjectBiochemical Phenomena, Metabolism, and Nutrition
dc.subjectCell Biology
dc.subjectCellular and Molecular Physiology
dc.subjectHemic and Immune Systems
dc.subjectImmunology and Infectious Disease
dc.subjectPhysiological Processes
dc.titleNeutrophil infiltration regulates clock-gene expression to organize daily hepatic metabolism
dc.typeJournal Article
dc.source.journaltitleeLife
dc.source.volume9
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=2906&amp;context=faculty_pubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/1886
dc.identifier.contextkey21291273
refterms.dateFOA2022-08-23T15:55:04Z
html.description.abstract<p>Liver 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.</p>
dc.identifier.submissionpathfaculty_pubs/1886
dc.contributor.departmentDavis Lab
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pagese59258


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Copyright © 2020, Crespo et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Except where otherwise noted, this item's license is described as Copyright © 2020, Crespo et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.