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- Title
Single-Cell RNA Sequencing Shows T-Cell Exhaustion Landscape in the Peripheral Blood of Patients with Hepatitis B Virus-Associated Acute-on-Chronic Liver Failure.
- Authors
Jia Yao; Yaqiu Ji; Tian Liu; Jinjia Bai; Han Wang; Ruoyu Yao; Juan Wang; Xiaoshuang Zhou
- Abstract
Background/Aims: The occurrence and development of hepatitis B virus-associated acute-onchronic liver failure (HBV-ACLF) is closely related to the immune pathway. We explored the heterogeneity of peripheral blood T cell subsets and the characteristics of exhausted T lymphocytes, in an attempt to identify potential therapeutic target molecules for immune dysfunction in ACLF patients. Methods: A total of 83,577 T cells from HBV-ACLF patients and healthy controls were screened for heterogeneity by single-cell RNA sequencing. In addition, exhausted T-lymphocyte subsets were screened to analyze their gene expression profiles, and their developmental trajectories were investigated. Subsequently, the expression of exhausted T cells and their capacity in secreting cytokines (interleukin 2, interferon γ, and tumor necrosis factor α) were validated by flow cytometry. Results: A total of eight stable clusters were identified, among which CD4+ TIGIT+ subset and CD8+ LAG-3+ subset, with high expression of exhaust genes, were significantly higher in the HBV-ACLF patients than in normal controls. As shown by pseudotime analysis, T cells experienced a transition from naïve T cells to effector T cells and then exhausted T cells. Flow cytometry confirmed that the CD4+TIGIT+ subset and CD8+LAG-3+ subset in the peripheral blood of the ACLF patients were significantly higher than those in the healthy controls. Moreover, in vitro cultured CD8+LAG-3+ T cells were significantly fewer capable of secreting cytokines than CD8+LAG-3- subset. Conclusions: Peripheral blood T cells are heterogeneous in HBV-ACLF. The exhausted T cells markedly increase during the pathogenesis of ACLF, suggesting that T-cell exhaustion is involved in the immune dysfunction of HBV-ACLF patients
- Subjects
T-cell exhaustion; RNA sequencing; HEPATITIS B; LIVER failure; LYMPHOCYTE subsets
- Publication
Gut & Liver, 2024, Vol 18, Issue 3, p520
- ISSN
1976-2283
- Publication type
Article
- DOI
10.5009/gnl220449