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Updated: Aug 23, 2025
Characterization of Immune Cell-derived Extracellular Vesicles and Studying Functional Impact on Cell Environment
Published on: June 2, 2020
Plasma Extracellular Vesicles Play a Role in Immune System Modulation in Minimal Hepatic Encephalopathy
Juan José Gallego1, Alessandra Fiorillo1, Franc Casanova-Ferrer1
1Fundación de Investigación Hospital Clínico Universitario de Valencia-INCLIVA, 46010 Valencia, Spain.
Abstract:
Minimal hepatic encephalopathy (MHE) is associated with changes in the immune system including an increased pro-inflammatory environment and altered differentiation of CD4+ T lymphocytes. The mechanisms remain unknown. Changes in extracellular vesicle (EV) cargo including proteins and miRNAs could play a main role as mediators of immune system changes associated with MHE. The aim was to assess whether plasma EVs from MHE patients played a role in inducing the pro-inflammatory environment and altered differentiation of CD4+ T lymphocyte subtypes in MHE patients. We characterized the miRNA and protein cargo of plasma EVs from 50 cirrhotic patients (27 without and 23 with MHE) and 24 controls. CD4+ T cells from the controls were cultured with plasma EVs from the three groups of study, and the cytokine release and differentiation to CD4+ T-cell subtypes were assessed. Plasma EVs from MHE patients had altered miRNA and protein contents, and were enriched in inflammatory factors compared to the controls and patients without MHE. EVs from MHE patients modulated the expression of pro-inflammatory IL-17, IL-21, and TNF-α and anti-inflammatory TGF-β in cultured CD4+ T lymphocytes, and increased the proportion of Th follicular and Treg cells and the activation of Th17 cells. In conclusion, plasma EVs could play an important role in the induction of immune changes observed in MHE.
Insights
Plasma extracellular vesicles (EVs) from patients with minimal hepatic encephalopathy (MHE) show altered cargo and promote inflammation. These EVs influence CD4+ T lymphocyte differentiation, suggesting a key role in MHE-associated immune changes.
Area of Science:
- Immunology
- Gastroenterology
- Cell Biology
Background:
- Minimal hepatic encephalopathy (MHE) involves immune system alterations, including inflammation and changes in CD4+ T lymphocytes.
- The precise mechanisms driving these immune changes in MHE are not fully understood.
- Extracellular vesicles (EVs) carrying proteins and miRNAs are potential mediators of immune dysregulation.
Purpose of the Study:
- To investigate the role of plasma EVs from MHE patients in inducing pro-inflammatory environments.
- To assess the impact of MHE-derived EVs on CD4+ T lymphocyte differentiation.
- To characterize the miRNA and protein cargo of plasma EVs in MHE.
Main Methods:
- Plasma EVs were isolated and characterized from cirrhotic patients with and without MHE, and healthy controls.
- CD4+ T cells from healthy donors were cultured with EVs from the study groups.
- Cytokine release and CD4+ T cell subtype differentiation (Th17, Treg) were analyzed.
Main Results:
- Plasma EVs from MHE patients exhibited distinct miRNA and protein profiles, enriched in inflammatory factors.
- MHE-derived EVs modulated pro-inflammatory (IL-17, IL-21, TNF-α) and anti-inflammatory (TGF-β) cytokine expression in CD4+ T cells.
- EVs from MHE patients increased the proportion of follicular T helper and regulatory T cells and enhanced Th17 cell activation.
Conclusions:
- Plasma EVs play a significant role in mediating immune system changes observed in minimal hepatic encephalopathy.
- Altered EV cargo in MHE contributes to a pro-inflammatory state and aberrant CD4+ T cell differentiation.
- Targeting EVs may offer a therapeutic strategy for immune dysregulation in MHE.
