ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1656692
This article is part of the Research TopicLiver Diseases – From Pathophysiology to New Treatment OptionsView all 5 articles
Extracellular vesicles of patients with acute-on-chronic liver failure induce mitochondrial dysfunction in T cells
Provisionally accepted
Mona-May Langer1
Sabrina Guckenbiehl2Alina Bauschen1
Helena Stadler1
Farnusch Kaschani2
Markus Kaiser2
Bernd Walkenfort2
Heiner Wedemeyer3
Christian M Lange1*- 1LMU Munich University Hospital, Munich, Germany
- 2Universitatsklinikum Essen, Essen, Germany
- 3Medizinische Hochschule Hannover, Hanover, Germany
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Background and Aims: Liver cirrhosis and in particular acute-on-chronic liver failure (ACLF) are characterized by systemic inflammation and dysfunctional immune responses. Extracellular vesicles (EVs) are important mediators of cell stress and inflammation, but their role in ACLF is unclear. Methods: Phenotype and immune function of EVs of patients with compensated liver cirrhosis, acute decompensation, or ACLF were characterized regarding particle size, concentration, surface markers, and RNA cargo. In addition, functional analyses were performed to assess the impact of EVs on T cells. Results: EVs of patients with liver cirrhosis showed lower expression of exosome-specific markers (e.g. CD9, CD63, CD81) than EVs of healthy individuals, carried a distinct cargo of proteins and small RNAs, and were in high frequency derived from liver cells based on their carriage of liver cell markers such as ASGPR1, CD248 or CD163. Of note, in ACLF the concentration of EVs decreased, and EVs in ACLF lost partially their differentiation and surface markers but were enriched in lncRNAs. In functional assays, EVs of patients with cirrhosis and ACLF induced changes in the composition of T cell populations like a loss of naïve and central memory T cells and an increase in effector memory T cells. Mechanistically, EVs decreased the viability of CD3+ T cells, which could be explained by an induction of mitochondrial dysfunction. Conclusion: Liver cirrhosis is associated with distinct changes in circulating EVs. In ACLF, EVs are less differentiated and induce mitochondrial dysfunction, decreased T cell viability and changes in the composition of T cell populations.
Keywords: systemic inflammation, Exosomes, t cell exhaustion, Organ failure, Livercirrhosis
Received: 30 Jun 2025; Accepted: 02 Sep 2025.
Copyright: © 2025 Langer, Guckenbiehl, Bauschen, Stadler, Kaschani, Kaiser, Walkenfort, Wedemeyer and Lange. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Christian M Lange, LMU Munich University Hospital, Munich, Germany
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