dc.contributor.author | Rolas, L | |
dc.contributor.author | Stein, M | |
dc.contributor.author | Barkaway, A | |
dc.contributor.author | Reglero, N | |
dc.contributor.author | Sciacca, E | |
dc.contributor.author | Yaseen, M | |
dc.contributor.author | Wang, H | |
dc.contributor.author | Vazquez-Martinez, L | |
dc.contributor.author | Golding, M | |
dc.contributor.author | Blacksell, IA | |
dc.contributor.author | Giblin, MJ | |
dc.contributor.author | Jaworska, E | |
dc.contributor.author | Bishop, CL | |
dc.contributor.author | Voisin, M | |
dc.contributor.author | Gaston-Massuet, C | |
dc.contributor.author | Fossati-Jimack, L | |
dc.contributor.author | Pitzalis, C | |
dc.contributor.author | Cooper, D | |
dc.contributor.author | Nightingale, TD | |
dc.contributor.author | Lopez-Otin, C | |
dc.contributor.author | Lewis, MJ | |
dc.contributor.author | Nourshargh, S | |
dc.date.accessioned | 2024-07-17T09:29:27Z | |
dc.date.available | 2024-06-07 | |
dc.date.available | 2024-07-17T09:29:27Z | |
dc.date.issued | 2024-06-25 | |
dc.identifier.issn | 1469-3178 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/98188 | |
dc.description.abstract | Cellular senescence is a hallmark of advanced age and a major instigator of numerous inflammatory pathologies. Whilst endothelial cell (EC) senescence is aligned with defective vascular functionality, its impact on fundamental inflammatory responses in vivo at single cell level remain unclear. To directly investigate the role of EC senescence on dynamics of neutrophil-venular wall interactions, we applied high resolution confocal intravital microscopy to inflamed tissues of an EC-specific progeroid mouse model, characterized by profound indicators of EC senescence. Progerin-expressing ECs supported prolonged neutrophil adhesion and crawling in a cell autonomous manner that additionally mediated neutrophil-dependent microvascular leakage. Transcriptomic and immunofluorescence analysis of inflamed tissues identified elevated levels of EC CXCL1 on progerin-expressing ECs and functional blockade of CXCL1 suppressed the dysregulated neutrophil responses elicited by senescent ECs. Similarly, cultured progerin-expressing human ECs exhibited a senescent phenotype, were pro-inflammatory and prompted increased neutrophil attachment and activation. Collectively, our findings support the concept that senescent ECs drive excessive inflammation and provide new insights into the mode, dynamics, and mechanisms of this response at single cell level. | en_US |
dc.language.iso | en | en_US |
dc.publisher | EMBO Press | en_US |
dc.relation.ispartof | EMBO Reports | |
dc.rights | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/ applies to the data associated with this article, unless otherwise stated in a credit line to the data, but does not extend to the graphical or creative elements of illustrations, charts, or figures. This waiver removes legal barriers to the re-use and mining of research data. According to standard scholarly practice, it is recommended to provide appropriate citation and attribution whenever technically possible. | |
dc.title | Senescent endothelial cells promote pathogenic neutrophil trafficking in inflamed tissues | en_US |
dc.type | Article | en_US |
dc.rights.holder | © 2024 The Author(s). | |
pubs.notes | Not known | en_US |
pubs.publication-status | Accepted | en_US |
pubs.publisher-url | https://doi.org/10.1038/s44319-024-00182-x | |
dcterms.dateAccepted | 2024-06-07 | |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |
qmul.funder | Neutrophils re-entering the circulation from a primary site of inflammation: Physiological or pathological?’::Wellcome Trust | en_US |
qmul.funder | Neutrophils re-entering the circulation from a primary site of inflammation: Physiological or pathological?’::Wellcome Trust | en_US |
rioxxterms.funder.project | b215eee3-195d-4c4f-a85d-169a4331c138 | en_US |