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Th17 cells in the liver: balancing autoimmunity and pathogen defense

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Abstract

In addition to carcinogenesis, T helper 17 (Th17) cells (a subtype of CD4 + T lymphocytes) are involved in the acute, chronic, and cirrhotic phases of liver diseases; however, their role in the development and progression of liver diseases remains unclear. It is difficult to elucidate the role of Th17 cells in liver diseases due to their dichotomous nature, i.e., plasticity in terms of pathogenic or host protective function depending on environmental and time phase factors. Moreover, insufficient depletion of Th17 cells by inhibiting the cytokines and transcription factors involved in their production causes difficulties in analyzing their specific role in vitro and in vivo murine models, partially due to complex interaction. This review summarizes the recent progress in understanding the plasticity and function of hepatic Th17 cells and type 3 cytokines.

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Abbreviations

AhR:

Aryl hydrocarbon receptor

AIH :

Autoimmune hepatitis

ALD:

Alcoholic liver diseases

α-SMA:

Alpha smooth muscle actin

ANA:

Antinuclear antibodies

ASMA:

Anti-smooth muscle antibodies

αGalCer:

Alpha-galactosylceramide

BATF :

Basic leucine zipper transcription factor ATF-like

Bcl:

B-cell lymphoma

BEC:

Biliary epithelial cell

CCL:

Chemokine CC motif ligand

CCR:

Chemokine CC motif receptor

CCl4 :

Carbon tetrachloride

Con A:

Concanavalin A

CRP:

C-reactive protein

CTLA:

Cytotoxic T-lymphocyte associated antigen

CXCL:

C-X-C motif chemokine ligand

CYP:

Cytochrome P450

DMIN:

3′3-Diindolylmethane

EAE:

Experimental autoimmune encephalomyelitis

FFA:

Free fatty acid

FGF:

Fibroblast growth factor

FICZ:

6-Formylindolo[3,2-b]carbazole

FMT:

Fecal microbiota transplantation

FOXP3:

Forkhead boxprotein P3

FXR:

Farnesoid X receptor

GaIN:

D-galactosamine

GM-CSF:

Granulocyte macrophage colony-stimulating factor

GWAS:

Genome-wide association study

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

HFD:

High-fat diet

HLA:

Human leukocyte antigen

HO:

Heme oxygenase

IBD:

Inflammatory bowel disease

ICAM:

Intracellular adhesion molecule

IFN:

Interferon

IL:

Interleukin

ILC:

Innate lymphoid cells

Ig:

Immunoglobulin

IRF4:

Interferon-regulatory factor 4

JAK:

Janus kinase

LC:

Liver cirrhosis

LCA:

Lithocholic acid

LPS:

Lipopolysaccharide

LSEC:

Liver sinusoidal endothelial cell

MAFLD:

Metabolic-associated fatty liver disease

MAIT:

Mucosal-associated invariant T

MAPK:

Mitogen-activated protein kinase

MCD:

Methionine–choline-deficient

MCL:

Myeloid-cell leukemia

MCP:

Monocyte chemoattractant protein

MIP:

Macrophage inflammatory protein

MMP:

Matrix metalloproteinase

MS:

Multiple sclerosis

NAFL:

Nonalcoholic fatty liver

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

NF-κB:

Nuclear factor kappa B

NK:

Natural killer

PBC:

Primary biliary cholangitis

PBMC:

Peripheral blood mononuclear cell

PSC:

Primary sclerosing cholangitis

RA:

Rheumatoid arthritis

RBP-J:

Recombination signal binding protein for immunoglobulin kappa J

Ref:

Redox factor

ROR :

Retinoic acid-related orphan receptor

SFB:

Segmented filamentous bacteria

SLE:

Systemic lupus erythematosus

STAT3:

Signal transducer and activator of transcription 3

S1P:

Sphingosine-1-phosphate

Tc:

Cytotoxic T

TGF-β:

Transforming growth factor-β

TGR5:

Takeda G protein-coupled receptor 5

Th :

Helper T

TNF:

Tumor necrosis factor

Treg:

Regulatory T

UC:

Ulcerative colitis

URI:

Unconventional prefoldin RPB5 interactor

VCAM:

Vascular cell adhesion molecule

VEGF:

Vascular endothelial growth factor

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Acknowledgements

We would like to thank Editage (www.editage.jp) for English language editing.

Funding

This study was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI (B) 20H04129 and Grant-in-Aid for Young Scientists (B) 20K17062; Japan Agency for Medical Research and Development (AMED) under Grant Number 21ek0109416h0003; the Takeda Science Foundation; and Keio University Medical Fund.

Japan Agency for Medical Research and Development,21ek0109416h0003,Nobuhiro Nakamoto,Japan Society for the Promotion of Science,20H04129,Nobuhiro Nakamoto,Takeda Science Foundation,School of Medicine,Keio University

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  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Shinanomachi, Tokyo, 160-8582, Japan

    Nobuhito Taniki, Nobuhiro Nakamoto, Po-Sung Chu, Masataka Ichikawa, Toshiaki Teratani & Takanori Kanai

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  1. Nobuhito Taniki
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Contributions

N.N. conceptualized this review. N.T. and N.N. wrote the manuscript and designed the figures. PS.C., T.I, T.T., and T.K. provided critical scientific advice and reviewed the manuscript. T.K. helped to conceive and supervise the study.

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This article is a contribution to the special issue on: Tolerance and autoimmunity in the liver—Guest Editor: Christoph Schramm, Ansgar Lohse & Ye Oo

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Taniki, N., Nakamoto, N., Chu, PS. et al. Th17 cells in the liver: balancing autoimmunity and pathogen defense. Semin Immunopathol 44, 509–526 (2022). https://doi.org/10.1007/s00281-022-00917-9

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