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

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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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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Authors and Affiliations

  1. Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa, 920-8641, Japan

    Takuya Seike, Eishiro Mizukoshi, Kazutoshi Yamada, Hikari Okada, Masaaki Kitahara, Tatsuya Yamashita, Kuniaki Arai, Takeshi Terashima, Noriho Iida, Kazumi Fushimi, Taro Yamashita, Yoshio Sakai, Masao Honda & Shuichi Kaneko

  2. Department of Human Pathology, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa, Japan

    Kenichi Harada

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  1. Takuya Seike
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Correspondence to Eishiro Mizukoshi.

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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

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