Enolase represents a metabolic checkpoint controlling the differential exhaustion programmes of hepatitis virus-specific CD8


Journal

Gut
ISSN: 1468-3288
Titre abrégé: Gut
Pays: England
ID NLM: 2985108R

Informations de publication

Date de publication:
10 2023
Historique:
received: 19 09 2022
accepted: 20 06 2023
medline: 15 9 2023
pubmed: 5 8 2023
entrez: 4 8 2023
Statut: ppublish

Résumé

Exhausted T cells with limited effector function are enriched in chronic hepatitis B and C virus (HBV and HCV) infection. Metabolic regulation contributes to exhaustion, but it remains unclear how metabolism relates to different exhaustion states, is impacted by antiviral therapy, and if metabolic checkpoints regulate dysfunction. Metabolic state, exhaustion and transcriptome of virus-specific CD8 HBV-specific (core Metabolism of HBV-specific and HCV-specific T cells is strongly connected to their exhaustion severity. Our results highlight enolase as metabolic regulator of severely exhausted T cells. They connect differential bioenergetic fitness with distinct exhaustion subtypes and varying liver disease, with implications for therapeutic strategies.

Identifiants

pubmed: 37541771
pii: gutjnl-2022-328734
doi: 10.1136/gutjnl-2022-328734
pmc: PMC10511960
doi:

Substances chimiques

Antiviral Agents 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1971-1984

Subventions

Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 100326/Z/12/Z
Pays : United Kingdom

Commentaires et corrections

Type : CommentIn

Informations de copyright

© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

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Auteurs

Frances Winkler (F)

Clinic for Internal Medicine II, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.
Faculty of Biology, University of Freiburg, Freiburg im Breisgau, Germany.

Anna V Hipp (AV)

Clinic for Internal Medicine II, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.

Carlos Ramirez (C)

Health Data Science Unit, Medical Faculty, University of Heidelberg, Heidelberg, Germany.

Bianca Martin (B)

Clinic for Internal Medicine II, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.

Matteo Villa (M)

Max Planck Institute of Immunobiology and Epigenetics, Freiburg im Breisgau, Germany.

Emilia Neuwirt (E)

Institute of Neuropathology, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.
Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg im Breisgau, Germany.

Oliver Gorka (O)

Institute of Neuropathology, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.

Jeroen Aerssens (J)

Translational Biomarkers, Infectious Diseases Therapeuic Area, Janssen Pharmaceutica, Beerse, Belgium.

Susanne E Johansson (SE)

Translational Biomarkers, Infectious Diseases Therapeuic Area, Janssen Pharmaceutica, Beerse, Belgium.

Nisha Rana (N)

Clinic for Internal Medicine II, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.

Sian Llewellyn-Lacey (S)

Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff University, Cardiff, UK.

David A Price (DA)

Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff University, Cardiff, UK.
Systems Immunity Research Institute, Cardiff University School of Medicine, Cardiff, UK.

Marcus Panning (M)

Institute of Virology, Freiburg University Medical Center, Faculty of Medicine, University Hospital Freiburg, Freiburg im Breisgau, Germany.

Olaf Groß (O)

Institute of Neuropathology, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.
Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg im Breisgau, Germany.

Erika L Pearce (EL)

The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA.

Carl M Hermann (CM)

Health Data Science Unit, Medical Faculty, University of Heidelberg, Heidelberg, Germany.

Kathrin Schumann (K)

Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich (TUM), Munich, Germany.

Luciana Hannibal (L)

Department of General Pediatrics, Laboratory of Clinical Biochemistry and Metabolism, Medical Center-University of Freiburg, Adolescent Medicine and Neonatology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Christoph Neumann-Haefelin (C)

Clinic for Internal Medicine II, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.

Tobias Boettler (T)

Clinic for Internal Medicine II, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.

Percy Knolle (P)

German Center for Infection Research (DZIF), Munich Partner Site, Munich, Germany.
Institute of Molecular Immunology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.

Maike Hofmann (M)

Clinic for Internal Medicine II, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.

Dirk Wohlleber (D)

Institute of Molecular Immunology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.

Robert Thimme (R)

Clinic for Internal Medicine II, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany.

Bertram Bengsch (B)

Clinic for Internal Medicine II, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg im Breisgau, Germany bertram.bengsch@uniklinik-freiburg.de.
Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg im Breisgau, Germany.
German Cancer Consortium (DKTK), Partner Site Freiburg, Heidelberg, Germany.

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Classifications MeSH