Abstract
Background
The interaction between T-cells/fatty acids involved in non-alcoholic fatty liver disease (NAFLD) and liver fibrosis progression is poorly understood. In this study, we conducted a comprehensive analysis of T-cell profiles of NAFLD patients to better understand their relationship with fatty acids and relevance to liver fibrosis.
Methods
We analyzed the differences in T-cell profiles of peripheral blood mononuclear cells (PBMCs) between 40 NAFLD patients and 5 healthy volunteers (HVs), and their relationship with liver fibrosis stage or progression. Moreover, we analyzed the relationship between T-cell profiles and fatty acid compositions in vivo, and changes in T-cell profiles after treatment with fatty acids in vitro.
Results
T-cell profiles of NAFLD patients were different from those of HVs. The CD25+CD45+CD4+ T-cell frequency was increased in NAFLD patients with high liver fibrosis stage and progression, and this indicated immune activation. Despite such a state of immune activation, the PD1+CD4+ T-cell frequency was decreased in the same patients group. The PD1+CD4+ T-cell frequency had a significantly negative correlation with the serum fatty acid composition ratio C16:1n7/C16:0. Moreover, the PD1+CD4+ T-cell frequency was significantly decreased by in vitro treatment with fatty acids. In addition, its rate of frequency change was significantly different between C16:0 and C16:1n7 and decreased by artificially increasing the C16:1n7/C16:0 ratio.
Conclusions
The analysis of PBMCs in NAFLD patients showed that T-cell profiles were different from those of HVs. And, it suggested that fatty acids modified T-cell profiles and were involved in liver fibrosis in NAFLD patients.
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Abbreviations
- NAFLD:
-
Non-alcoholic fatty liver disease
- NASH:
-
Non-alcoholic steatohepatitis
- CD:
-
Cluster of differentiation
- PBMCs:
-
Peripheral blood mononuclear cells
- NAS:
-
NAFLD activity score
- RPMI:
-
Roswell Park Memorial Institute
- FSC:
-
Fetal calf serum
- Treg :
-
Regulatory T-cell
- FoxP3:
-
Forkhead box P3
- T-bet:
-
T-box expressed in T-cells
- RORγt:
-
Retinoic acid-related orphan receptor gamma t
- Th:
-
T-helper
- CTLA-4:
-
Cytotoxic T-lymphocyte-associated protein 4
- PD-1:
-
Programmed death 1
- CXCR3:
-
C-X-C motif chemokine receptor 3
- CCR4:
-
C–C motif chemokine receptor 4
- IHC:
-
Immunohistochemistry
- DAPI:
-
4′6-Diamidino-2-phenylindole
- NAFL:
-
Non-alcoholic fatty liver
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Seike, T., Mizukoshi, E., Yamada, K. et al. Fatty acid-driven modifications in T-cell profiles in non-alcoholic fatty liver disease patients. J Gastroenterol 55, 701–711 (2020). https://doi.org/10.1007/s00535-020-01679-7
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DOI: https://doi.org/10.1007/s00535-020-01679-7