Differential roles for the oxygen sensing enzymes PHD1 and PHD3 in the regulation of neutrophil metabolism and function.

Hypoxia Inflammation Neutrophil PHD1 PHD3 Prolyl hydroxylase

Journal

Wellcome open research
ISSN: 2398-502X
Titre abrégé: Wellcome Open Res
Pays: England
ID NLM: 101696457

Informations de publication

Date de publication:
2023
Historique:
accepted: 06 08 2024
medline: 11 9 2024
pubmed: 11 9 2024
entrez: 11 9 2024
Statut: epublish

Résumé

Neutrophils are essential in the early innate immune response to pathogens. Harnessing their antimicrobial powers, without driving excessive and damaging inflammatory responses, represents an attractive therapeutic possibility. The neutrophil population is increasingly recognised to be more diverse and malleable than was previously appreciated. Hypoxic signalling pathways are known to regulate important neutrophil behaviours and, as such, are potential therapeutic targets for regulating neutrophil antimicrobial and inflammatory responses. We used a combination of We found that PHD1 deficiency drives alterations in neutrophil metabolism and recruitment, in an oxygen dependent fashion. Despite this, PHD1 deficiency did not significantly alter PHD3 deficiency drives a favourable neutrophil phenotype in infection and, as such, is an important potential therapeutic target.

Sections du résumé

Background UNASSIGNED
Neutrophils are essential in the early innate immune response to pathogens. Harnessing their antimicrobial powers, without driving excessive and damaging inflammatory responses, represents an attractive therapeutic possibility. The neutrophil population is increasingly recognised to be more diverse and malleable than was previously appreciated. Hypoxic signalling pathways are known to regulate important neutrophil behaviours and, as such, are potential therapeutic targets for regulating neutrophil antimicrobial and inflammatory responses.
Methods UNASSIGNED
We used a combination of
Results UNASSIGNED
We found that PHD1 deficiency drives alterations in neutrophil metabolism and recruitment, in an oxygen dependent fashion. Despite this, PHD1 deficiency did not significantly alter
Conclusions UNASSIGNED
PHD3 deficiency drives a favourable neutrophil phenotype in infection and, as such, is an important potential therapeutic target.

Identifiants

pubmed: 39257914
doi: 10.12688/wellcomeopenres.19915.2
pmc: PMC11384204
doi:

Banques de données

figshare
['10.6084/m9.figshare.24106686.v4']

Types de publication

Journal Article

Langues

eng

Pagination

569

Informations de copyright

Copyright: © 2024 Watts E et al.

Déclaration de conflit d'intérêts

No competing interests were disclosed.

Auteurs

Emily Watts (E)

Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, Scotland, EH16 4UU, UK.

Joseph Willison (J)

Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, Scotland, EH16 4UU, UK.

Simone Arienti (S)

Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, Scotland, EH16 4UU, UK.

Pranvera Sadiku (P)

Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, Scotland, EH16 4UU, UK.

Patricia Coelho (P)

Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, Scotland, EH16 4UU, UK.

Manuel Sanchez-Garcia (M)

Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, Scotland, EH16 4UU, UK.

Ailiang Zhang (A)

Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, Scotland, EH16 4UU, UK.

Fiona Murphy (F)

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, Scotland, G4 0RE, UK.

Rebecca Dickinson (R)

Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, Scotland, EH16 4UU, UK.

Ananda Mirchandani (A)

Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, Scotland, EH16 4UU, UK.

Tyler Morrison (T)

Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, Scotland, EH16 4UU, UK.

Amy Lewis (A)

The Bateson Centre, Department of Infection and Immunity and Cardiovascular Disease, The University of Sheffield, Sheffield, England, S10 2TN, UK.

Wesley Vermaelen (W)

Laboratory of Applied Mass Spectrometry, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Flanders, Belgium.
Metabolomics Core Facility, Vlaams Instituut voor Biotechnologie KU Leuven Center for Cancer Biology, Leuven, Flanders, Belgium.

Bart Ghesquiere (B)

Laboratory of Applied Mass Spectrometry, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Flanders, Belgium.
Metabolomics Core Facility, Vlaams Instituut voor Biotechnologie KU Leuven Center for Cancer Biology, Leuven, Flanders, Belgium.

Peter Carmeliet (P)

Laboratory of Angiogenesis and Vascular Metabolism, Vlaams Instituut voor Biotechnologie KU Leuven Center for Cancer Biology, Leuven, Flanders, Belgium.

Massimilliano Mazzone (M)

Laboratory of Tumor Inflammation and Angiogenesis (VIB-KU Leuven), KU Leuven, Leuven, Flanders, Belgium.

Patrick Maxwell (P)

School of Clinical Medicine, University of Cambridge, Cambridge, England, UK.

Christopher Pugh (C)

Nuffield Department of Medicine, University of Oxford, Oxford, England, UK.

David Dockrell (D)

Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, Scotland, EH16 4UU, UK.

Moira Whyte (M)

Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, Scotland, EH16 4UU, UK.

Sarah Walmsley (S)

Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, Scotland, EH16 4UU, UK.

Classifications MeSH