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Distinct immunometabolic signatures in circulating immune cells define disease outcome in acute-on-chronic liver failure.
Feio-Azevedo, Rita; Boesch, Markus; Radenkovic, Silvia; van Melkebeke, Lukas; Smets, Lena; Wallays, Marie; Boeckx, Bram; Philips, Gino; Prata de Oliveira, Janaíne; Ghorbani, Mohammad; Laleman, Wim; Meersseman, Philippe; Wilmer, Alexander; Cassiman, David; van Malenstein, Hannah; Triantafyllou, Evangelos; Sánchez, Cristina; Aguilar, Ferran; Nevens, Frederik; Verbeek, Jef; Moreau, Richard; Arroyo, Vicente; Denadai Souza, Alexandre; Clària, Joan; Lambrechts, Diether; Ghesquière, Bart; Korf, Hannelie; van der Merwe, Schalk.
Afiliación
  • Feio-Azevedo R; Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium.
  • Boesch M; Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium.
  • Radenkovic S; Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium.
  • van Melkebeke L; Metabolomics Expertise Center, Center for Cancer Biology, VIB Center for Cancer Biology, Leuven, Belgium.
  • Smets L; Department of Oncology, Metabolomics Expertise Center, KU Leuven, Leuven, Belgium.
  • Wallays M; Department of Clinical Genomics, Mayo Clinic, Rochester, Minnesota, USA.
  • Boeckx B; Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium.
  • Philips G; Department of Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium.
  • Prata de Oliveira J; Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium.
  • Ghorbani M; Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium.
  • Laleman W; Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium.
  • Meersseman P; VIB Center for Cancer Biology, Leuven, Belgium.
  • Wilmer A; Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium.
  • Cassiman D; VIB Center for Cancer Biology, Leuven, Belgium.
  • van Malenstein H; Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium.
  • Triantafyllou E; Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
  • Sánchez C; Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium.
  • Aguilar F; Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium.
  • Nevens F; Department of Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium.
  • Verbeek J; Department of Internal Medicine, UZ Leuven, KU Leuven, Leuven, Belgium.
  • Moreau R; Department of Internal Medicine, UZ Leuven, KU Leuven, Leuven, Belgium.
  • Arroyo V; Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium.
  • Denadai Souza A; Metabolomics Expertise Center, Center for Cancer Biology, VIB Center for Cancer Biology, Leuven, Belgium.
  • Clària J; Department of Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium.
  • Lambrechts D; Laboratory of Hepatology, CHROMETA Department, KU Leuven, Leuven, Belgium.
  • Ghesquière B; Department of Gastroenterology and Hepatology, UZ Leuven, Leuven, Belgium.
  • Korf H; Section of Hepatology and Gastroenterology, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
  • van der Merwe S; European Foundation for the Study of Chronic Liver Failure, EF-CLIF, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain.
Hepatology ; 2024 May 16.
Article en En | MEDLINE | ID: mdl-38761406
ABSTRACT
BACKGROUND AND

AIMS:

Acute-on-chronic liver failure (ACLF) is a complication of cirrhosis characterized by multiple organ failure and high short-term mortality. The pathophysiology of ACLF involves elevated systemic inflammation leading to organ failure, along with immune dysfunction that heightens susceptibility to bacterial infections. However, it is unclear how these aspects are associated with recovery and nonrecovery in ACLF. APPROACH AND

RESULTS:

Here, we mapped the single-cell transcriptome of circulating immune cells from patients with ACLF and acute decompensated (AD) cirrhosis and healthy individuals. We further interrogate how these findings, as well as immunometabolic and functional profiles, associate with ACLF-recovery (ACLF-R) or nonrecovery (ACLF-NR). Our analysis unveiled 2 distinct states of classical monocytes (cMons). Hereto, ACLF-R cMons were characterized by transcripts associated with immune and stress tolerance, including anti-inflammatory genes such as RETN and LGALS1 . Additional metabolomic and functional validation experiments implicated an elevated oxidative phosphorylation metabolic program as well as an impaired ACLF-R cMon functionality. Interestingly, we observed a common stress-induced tolerant state, oxidative phosphorylation program, and blunted activation among lymphoid populations in patients with ACLF-R. Conversely, ACLF-NR cMon featured elevated expression of inflammatory and stress response genes such as VIM , LGALS2 , and TREM1 , along with blunted metabolic activity and increased functionality.

CONCLUSIONS:

This study identifies distinct immunometabolic cellular states that contribute to disease outcomes in patients with ACLF. Our findings provide valuable insights into the pathogenesis of ACLF, shedding light on factors driving either recovery or nonrecovery phenotypes, which may be harnessed as potential therapeutic targets in the future.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Hepatology Año: 2024 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Hepatology Año: 2024 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Estados Unidos