Fatty acid-driven modifications in T-cell profiles in non-alcoholic fatty liver disease patients

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.

Keywords: Fatty acid; Immune cell; Lymphocyte; NAFLD; NASH.