• ScRNA‐seq
• hepatic stellate cell
• heterogeneity
• intercellular crosstalk
• liver fibrosis
• macrophage

• National Natural Science Foundation of China

• translational research
• non-alcoholic fatty liver disease

• Humans
• Male
• Animals
• Mice
• Middle Aged
• Aged
• Female
• Non-alcoholic Fatty Liver Disease
• Diabetes Mellitus, Type 2/complications
• Insulin Resistance
• Leukocytes, Mononuclear
• T-Cell Exhaustion
• Liver Cirrhosis
• Disease Models, Animal

• National Research Foundation of Korea (NRF)

• GPCR signaling
• fibroblast behavior
• fibrotic diseases
• functional heterogeneity
• pathophysiology
• pharmacological targeting

• Humans
• Receptors, G-Protein-Coupled/metabolism
• Signal Transduction
• Fibroblasts/metabolism
• Neoplasms
• Fibrosis

• R01 CA247471 NCI NIH HHS
• R44 DK117472 NIDDK NIH HHS
• U01 CA210240 NCI NIH HHS
• I01 BX004676 BLRD VA
• P01 CA217798 NCI NIH HHS
• U01 CA200466 NCI NIH HHS
• I01 BX001786 BLRD VA
• R01 CA195586 NCI NIH HHS
• U01 CA213862 NCI NIH HHS

• bioluminescence imaging (BLI)
• carbon tetrachloride (CCl4)
• liver cirrhosis
• natural killer (NK) cells

• NRF-2020R1A2C2011695 National Research Foundation of Korea
• 2020R1A2C2011428 National Research Foundation of Korea
• 2022R1F1A1069854 National Research Foundation of Korea

• Co-culture
• Density gradient centrifugation
• Flow cytometry
• Hepatic stellate cells
• Lymphocytes

• biomarkers
• chronic hepatitis
• fibrosis
• liver cirrhosis
• mac-2 binding protein glycosylation isomer

• Antigens, Neoplasm
• Aspartate Aminotransferases
• Biomarkers
• Glycosylation
• Humans
• Liver Cirrhosis/complications
• Liver Diseases/complications
• Membrane Glycoproteins
• Retrospective Studies
• gamma-Glutamyltransferase/metabolism

• Acetaldehyde
• Alcoholic liver disease
• Fatty acid ethyl esters
• Interorgan communication
• Non-oxidative alcohol metabolites
• Oxidative alcohol metabolites

• gene expression profiling
• inflammation
• liver neoplasms
• lymphocytes, tumor-infiltrating

• Wisteria floribunda agglutinin (WFA)
• Glyco-RIDGE
• M2BP glycosylation isomer
• hepatitis
• liver cirrhosis

• Antigens, Neoplasm/blood
• Antigens, Neoplasm/chemistry
• Biomarkers, Tumor/blood
• Biomarkers, Tumor/chemistry
• HEK293 Cells
• Healthy Volunteers
• Humans
• Liver Cirrhosis/blood
• Plant Lectins/blood
• Plant Lectins/chemistry
• Polysaccharides/blood
• Polysaccharides/chemistry
• Protein Array Analysis
• Receptors, N-Acetylglucosamine/blood
• Receptors, N-Acetylglucosamine/chemistry
• Recombinant Proteins/blood
• Recombinant Proteins/chemistry

• Carnitine
• Fatty Liver
• Humans

• CXCR3
• IFNγ
• NAFLD
• PKM
• T cell
• TNF
• cellular metabolism
• glycolysis
• liver
• obesity

• Animals
• Carrier Proteins/immunology
• Cell Line
• Female
• Humans
• Male
• Membrane Proteins/immunology
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Non-alcoholic Fatty Liver Disease/immunology
• Pyruvate Kinase/immunology
• Receptors, CXCR3/immunology
• Th17 Cells/cytology
• Th17 Cells/immunology
• Thyroid Hormones/immunology
• Thyroid Hormone-Binding Proteins

• P30 DK078392 NIDDK NIH HHS
• T32 GM063483 NIGMS NIH HHS
• R21 AI139829 NIAID NIH HHS
• R01 DK099222 NIDDK NIH HHS
• T32 AI118697 NIAID NIH HHS

To investigate the mechanisms of Fuzheng Huayu (FZHY) Capsule in the treatment of hepatitis B (HBV)- associated fibrosis, HBV patients were divided into two groups, 50 cases were in the nucleotide analogues (NAs) group, while additional 50 cases were in the NAs + FZHY group.

We assessed the curative effects of antifibrosis through liver function, FibroScan test, and liver biopsy and detected the ratio of lymphocyte subsets by flow cytometry. Peripheral blood lymphocyte and CD8⁺T, CD4⁺T, and natural killer cell subsets collected from patients were cocultured with LX-2 cells. Activation of LX-2 cells, production of the extracellular matrix, apoptosis, and proliferation of LX-2 cells were determined. Chronic liver injury models were established by ConA treatment.

It is evident that FZHY treatment significantly increased the percentage of NK cells, the rate of death, and apoptosis of LX-2 cells and decreased the FibroScan liver stiffness measurement value. The expressions of α-SMA and procollagen type I mRNA in LX-2 cells of the FZHY treatment group as downregulated when they were cocultured with lymphocytes compared to those from the NAs group. The proliferation of LX-2 cells in the FZHY treatment group was inhibited compared to that in the NAs group. In a mouse model of hepatic fibrosis, PBLs and IHLs from ConA exposure plus FZHY treatment inhibited the ability of JS-1 cells to express α-SMA.

FZHY Capsule improved the disordered cellular immunity and postponed liver fibrosis possibly through inhibiting the interaction between lymphocyte and hepatic stellate cells.

• Apoptosis
• Cyclin
• E Cell cycle
• Hedgehog signaling
• NAFLD
• NASH
• TLR4
• p21
• p53

Lactose-based prebiotics are synthesized by enzymatic- or microbial- biotransformation of lactose and have unique functional values. In this comprehensive review article, the biochemical mechanisms of controlling osteoporosis, blood-lipid, and glucose levels by lactose-based prebiotics and symbiosis with probiotics are reported along with the results of clinical investigations. Interaction between lactose-based prebiotics and probiotics reduces osteoporosis by (a) transforming insoluble inorganic salts to soluble and increasing their absorption to gut wall; (b) maintaining and protecting mineral absorption surface in the intestine; (c) increasing the expression of calcium-binding proteins in the gut wall; (d) remodeling osteoclasts and osteoblasts formation; (e) releasing bone modulating factors; and (f) degrading mineral complexing phytic acid. Lactose-based prebiotics with probiotics control lipid level in the bloodstream and tissue by (a) suppressing the expressions of lipogenic- genes and enzymes; (b) oxidizing fatty acids in muscle, liver, and adipose tissue; (c) binding cholesterol with cell membrane of probiotics and subsequent assimilation by probiotics; (d) enzymatic-transformations of bile acids; and (e) converting cholesterol to coprostanol and its defecation. Symbiosis of lactose-based prebiotics with probiotics affect plasma glucose level by (a) increasing the synthesis of gut hormones plasma peptide-YY, glucagon-like peptide-1 and glucagon-like peptide-2 from entero-endocrine L-cells; (b) altering glucose assimilation and metabolism; (c) suppressing systematic inflammation; (d) reducing oxidative stress; and (e) producing amino acids. Clinical investigations show that lactose-based prebiotic galacto-oligosaccharide improves mineral absorption and reduces hyperlipidemia. Another lactose-based prebiotic, lactulose, improves mineral absorption, and reduces hyperlipidemia and hyperglycemia. It is expected that this review article will be of benefit to food technologists and medical practitioners.

• blood glucose level
• blood lipid level
• lactose-based prebiotics
• osteoporosis
• probiotics

• Adolescent
• Adult
• Gastrointestinal Agents/therapeutic use
• Gastrointestinal Microbiome/physiology
• Humans
• Hyperglycemia/diet therapy
• Hyperglycemia/metabolism
• Hyperlipidemias/diet therapy
• Hyperlipidemias/metabolism
• Lactose/administration & dosage
• Lactose/adverse effects
• Lactulose/therapeutic use
• Male
• Middle Aged
• Osteoporosis/diet therapy
• Osteoporosis/metabolism
• Prebiotics/administration & dosage
• Prebiotics/adverse effects
• Probiotics/adverse effects
• Probiotics/therapeutic use
• Young Adult

• Animals
• Anti-Inflammatory Agents
• Bile Acids and Salts/metabolism
• Chemical and Drug Induced Liver Injury/drug therapy
• Chemical and Drug Induced Liver Injury/etiology
• Chemical and Drug Induced Liver Injury/pathology
• Endotoxins/toxicity
• Inflammation/chemically induced
• Inflammation/drug therapy
• Inflammation/pathology
• Lipopolysaccharides/toxicity
• Lysophospholipids/pharmacology
• Male
• Mice
• Mice, Inbred C57BL
• RAW 264.7 Cells
• Tumor Necrosis Factor-alpha/metabolism
• Ursodeoxycholic Acid/analogs & derivatives
• Ursodeoxycholic Acid/pharmacology

• Deutsche Forschungsgemeinschaft
• Universität Heidelberg

Interleukin (IL)-33 has been recently reported to be strongly pro-fibrogenic in various models of liver disease. Our aim was to study the role of endogenous IL-33 in a diet-induced model of steatohepatitis. IL-33 deficient mice and wild type (WT) littermates received a high-fat diet (HFD), or a standard diet for 12 weeks. The HFD-induced steatohepatitis was associated with an upregulation of IL-33 transcripts and protein. An insulin tolerance test revealed lower systemic insulin sensitivity in IL-33-/—HFD mice than in WT-HFD mice. Nevertheless, IL-33 deficiency did not affect the severity of liver inflammation by histological and transcriptomic analyses, nor the quantity of liver fibrosis. Livers from HFD mice had more myeloid populations, markedly fewer NKT cells and higher proportion of ST2+ Treg cells and ST2+ type 2 innate lymphoid cells (ILC2), all unaffected by IL-33 deficiency. In conclusion, deficiency of endogenous IL-33 does not affect the evolution of experimental diet-induced steatohepatitis towards liver fibrosis.

• NAFLD
• NASH
• immune cells
• nonalcoholic fatty liver disease
• nonalcoholic steatohepatitis

Lactose-derived prebiotics provide wide ranges of gastrointestinal comforts. In this review article, the probable biochemical mechanisms through which lactose-derived prebiotics offer positive gastrointestinal health are reported along with the up-to-date results of clinical investigations; this might be the first review article of its kind, to the best of our knowledge. Lactose-derived prebiotics have unique biological and functional values, and they are confirmed as ‘safe’ by the Food and Drug Administration federal agency. Medical practitioners frequently recommend them as therapeutics as a pure form or combined with dairy-based products (yoghurt, milk and infant formulas) or fruit juices. The biological activities of lactose-derived prebiotics are expressed in the presence of gut microflora, mainly probiotics (Lactobacillus spp. in the small intestine and Bifidobacterium spp. in the large intestine). Clinical investigations reveal that galacto-oligosaccharide reduces the risks of several types of diarrhea (traveler’s diarrhea, osmotic diarrhea and Clostridium difficile associated relapsing diarrhea). Lactulose and lactosucrose prevent inflammatory bowel diseases (Crohn’s disease and ulcerative colitis). Lactulose and lactitol reduce the risk of hepatic encephalopathy. Furthermore, lactulose, galacto-oligosaccharide and lactitol prevent constipation in individuals of all ages. It is expected that the present review article will receive great attention from medical practitioners and food technologists.

• biological activities
• gastrointestinal health
• lactose-derived prebiotics
• probiotics

• Cathartics/therapeutic use
• Colonic Neoplasms/prevention & control
• Constipation/prevention & control
• Diarrhea/microbiology
• Diarrhea/therapy
• Galactosides/therapeutic use
• Gastrointestinal Diseases/prevention & control
• Gastrointestinal Tract/drug effects
• Gastrointestinal Tract/microbiology
• Hepatic Encephalopathy/prevention & control
• Humans
• Inflammatory Bowel Diseases/prevention & control
• Lactose/chemistry
• Lactulose/therapeutic use
• Oligosaccharides/therapeutic use
• Prebiotics
• Probiotics/pharmacology
• Probiotics/therapeutic use
• Sugar Alcohols/therapeutic use
• Trisaccharides/therapeutic use

Exemestane (EXE) is an irreversible steroidal aromatase inhibitor mainly used as an adjuvant endocrine therapy for postmenopausal women suffering from breast cancer. Besides inhibiting aromatase activity, EXE has multiple biological functions, such as antiproliferation, anti-inflammatory, and antioxidant activities which are all involved in hepatic fibrosis. Therefore, we investigated the role of EXE during the progress of hepatic fibrosis. The effect of EXE on liver injury and fibrosis were assessed in two hepatic fibrosis rat models, which were induced by either carbon tetrachloride (CCl₄) or bile duct ligation (BDL). The influence of EXE treatment on activation and proliferation of primary rat hepatic stellate cells (HSCs) was observed in vitro. The results showed that EXE attenuated the liver fibrosis by decreasing the collagen deposition and α-SMA expression in vivo and inhibited the activation and proliferation of primary rat HSCs in vitro. Additionally, EXE promoted the secretion of antifibrotic and anti-inflammatory cytokine IL-10 in vivo and in HSC-T6 culture media. In conclusion, our findings reveal a new function of EXE on hepatic fibrosis and prompted its latent application in liver fibrotic-related disease.

Growth differentiation factor 15 (GDF15) has recently been shown to have an important role in the regulation of mitochondrial function and in the pathogenesis of complex human diseases. Nevertheless, the role of GDF15 in alcohol-induced or fibrotic liver diseases has yet to be determined. In this study, we demonstrate that alcohol- or carbon tetrachloride (CCl₄)-mediated hepatic GDF15 production ameliorates liver inflammation and fibrosis. Alcohol directly enhanced GDF15 expression in primary hepatocytes, which led to increased oxygen consumption. Moreover, GDF15 reduced the expression of pro-inflammatory cytokines in liver-resident macrophages, leading to an improvement in inflammation and fibrosis in the liver. GDF15 knockout (KO) mice had more TNF-α-producing T cells and more activated CD4⁺ and CD8⁺ T cells in the liver than wild-type mice. Liver-infiltrating monocytes and neutrophils were also increased in the GDF15 KO mice during liver fibrogenesis. These changes in hepatic immune cells were associated with increased tissue inflammation and fibrosis. Finally, recombinant GDF15 decreased the expression of pro-inflammatory cytokines and fibrotic mediators and prevented the activation of T cells in the livers of mice with CCl₄-induced liver fibrosis. These results suggest that GDF15 could be a potential therapeutic target for the treatment of alcohol-induced and fibrotic liver diseases.

• Biomarker
• CD4+ T cell
• Fibrosis
• Human immunodeficiency virus/hepatitis C virus-coinfection
• Natural killer cells

Many types of innate (natural killer cells, natural killer T cells, and Kupffer cells/macrophages) and adaptive (T cells and B cells) immune cells are enriched within the liver and function in liver physiology and pathology. Liver pathology is generally induced by two types of immunologic insults: failure to eliminate antigens derived from the gastrointestinal tract which are important for host defense and an impaired tissue protective tolerance mechanism that helps reduce the negative outcomes of immunopathology. Accumulating evidence from the last several decades suggests that hepatic immune cells play an important role in the pathogenesis of alcoholic and nonalcoholic liver injury and inflammation in humans and mice. Here, we focus on the roles of innate and adaptive immune cells in the development and maintenance of alcoholic liver disease and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Additionally, the pathogenesis of liver disease and new therapeutic targets for preventing and treating alcoholic liver disease and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis are discussed.

• Kupffer cells
• M2BPGi
• Mac-2
• WFA+-M2BP
• hepatic stellate cells

• BMPs
• Liver fibrosis
• Stellate cells
• Targeted delivery
• siRNA

• Hepatic Stellate Cells/pathology
• Humans
• Liver Cirrhosis/pathology
• Liver Cirrhosis/therapy
• Nanoparticles/administration & dosage
• Polymers/administration & dosage
• RNA Interference
• RNA, Small Interfering/therapeutic use

• Animals
• Carbon Tetrachloride Poisoning/metabolism
• Exosomes
• Hepatic Stellate Cells/metabolism
• Interleukin-17/metabolism
• Liver Cirrhosis/metabolism
• Male
• Mice, Inbred C57BL
• Mice, Transgenic
• Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism
• Receptors, Antigen, T-Cell, gamma-delta/metabolism
• T-Lymphocytes/metabolism
• Toll-Like Receptor 3/metabolism

Emerging evidence revealed that diabetes induces abnormal immune responses that result in serious complications in organs. However, the effect of hyperglycemia on hepatic immunity remains obscure. We evaluated the population and function of hepatic immune cells in streptozotocin (STZ)-induced hyperglycemic mice. CC chemokine receptor 2 (CCR2)-knockout mice and mice with a depletion of regulatory T cells (DEREG) were used to investigate the migration and role of regulatory T cells (Tregs) in hyperglycemic mice. The inflammatory cytokines and hepatic transaminase levels were significantly increased in the hyperglycemic mice. The population and number of infiltrating monocytes, granulocytes, and Tregs were enhanced in the livers of the hyperglycemic mice. Hepatic monocytes other than macrophages showed the increased expression of inflammatory cytokines and chemokines in the hyperglycemic mice. The CCR2 knockout and DEREG chimeric mice exhibited increased populations of activated T cells and neutrophils compared to the WT chimeric mice, which promoted hepatic inflammation in the hyperglycemic mice. The migration of CCR2 knockout Tregs into the liver was significantly reduced compared to the WT Tregs. We demonstrated that hyperglycemia contributes to increase in infiltrating monocytes and Tregs, which are associated with hepatic immune dysfunction in mice. CCR2-mediated migration of Tregs regulates hyperglycemia-induced hepatic inflammation.

Chronic alcohol consumption is one of the most common causes of the progression of alcoholic liver disease (ALD). In the past, alcohol-mediated hepatocyte injury was assumed to be a significantly major cause of ALD. However, a huge number of recent and brilliant studies have demonstrated that hepatic non-parenchymal cells including Kupffer cells, hepatic stellate cells, liver sinusoidal endothelial cells and diverse types of lymphocytes play crucial roles in the pathogenesis of ALD by producing inflammatory mediators such as cytokines, oxidative stress, microRNA, and lipid-originated metabolites (retinoic acid and endocannabinoids) or by directly interacting with parenchymal cells (hepatocytes). Therefore, understanding the comprehensive roles of hepatic non-parenchymal cells during the development of ALD will provide new integrative directions for the treatment of ALD. This review will address the roles of non-parenchymal cells in alcoholic steatosis, inflammation, and liver fibrosis and might help us to discover possible therapeutic targets and treatments involving modulating the non-parenchymal cells in ALD.

• Alcoholic liver disease
• Reactive oxygen stress
• Endocannabinoid
• NADPH oxidase

• Animals
• Anti-Inflammatory Agents/therapeutic use
• Antioxidants/therapeutic use
• Hepatic Stellate Cells/drug effects
• Hepatic Stellate Cells/immunology
• Hepatic Stellate Cells/metabolism
• Hepatic Stellate Cells/pathology
• Humans
• Inflammation Mediators/metabolism
• Kupffer Cells/drug effects
• Kupffer Cells/immunology
• Kupffer Cells/metabolism
• Kupffer Cells/pathology
• Liver/drug effects
• Liver/immunology
• Liver/metabolism
• Liver/pathology
• Liver Diseases, Alcoholic/drug therapy
• Liver Diseases, Alcoholic/immunology
• Liver Diseases, Alcoholic/metabolism
• Liver Diseases, Alcoholic/pathology
• Oxidative Stress
• Reactive Oxygen Species/metabolism
• Signal Transduction

Accumulating evidence suggests that retinol and its metabolites are closely associated with liver fibrogenesis. Recently, we demonstrated that genetic ablation of alcohol dehydrogenase 3 (ADH3), a retinol metabolizing gene that is expressed in hepatic stellate cells (HSCs) and natural killer (NK) cells, attenuated liver fibrosis in mice. In the current study, we investigated whether pharmacological ablation of ADH3 has therapeutic effects on experimentally induced liver fibrosis in mice.

Liver fibrosis was induced by intraperitoneal injections of carbon tetrachloride (CCl₄) or bile duct ligation (BDL) for two weeks. To inhibit ADH3-mediated retinol metabolism, 10 μg 4-methylpyrazole (4-MP)/g of body weight was administered to mice treated with CCl₄ or subjected to BDL. The mice were sacrificed at week 2 to evaluate the regression of liver fibrosis. Liver sections were stained for collagen and α-smooth muscle actin (α-SMA). In addition, HSCs and NK cells were isolated from control and treated mice livers for molecular and immunological studies.

Treatment with 4-MP attenuated CCl₄- and BDL-induced liver fibrosis in mice, without any adverse effects. HSCs from 4-MP treated mice depicted decreased levels of retinoic acids and increased retinol content than HSCs from control mice. In addition, the expression of α-SMA, transforming growth factor-β1 (TGF-β1), and type I collagen α1 was significantly reduced in the HSCs of 4-MP treated mice compared to the HSCs from control mice. Furthermore, inhibition of retinol metabolism by 4-MP increased interferon-γ production in NK cells, resulting in increased apoptosis of activated HSCs.

Based on our data, we conclude that inhibition of retinol metabolism by 4-MP ameliorates liver fibrosis in mice through activation of NK cells and suppression of HSCs. Therefore, retinol and its metabolizing enzyme, ADH3, might be potential targets for therapeutic intervention of liver fibrosis.

• Copper
• Fibrosis
• Inflammation
• Liver
• Nonalcoholic steatohepatitis
• Steatosis

• Diagnosis
• Epidemiology
• Genetics
• Insulin resistance
• Management
• Metabolic syndrome
• Non-alcoholic fatty liver disease
• Pathogenesis
• Prognosis

• Comorbidity
• Disease Progression
• Genetic Predisposition to Disease
• Humans
• Non-alcoholic Fatty Liver Disease/diagnosis
• Non-alcoholic Fatty Liver Disease/etiology
• Non-alcoholic Fatty Liver Disease/mortality
• Non-alcoholic Fatty Liver Disease/therapy
• Predictive Value of Tests
• Risk Factors
• Treatment Outcome

• Cirrhosis
• Extracellular matrix
• Fibrogenesis
• Hepatic stellate cells
• Liver
• Liver fibrosis
• Myofibroblast

• Animals
• Cell Proliferation
• Cytokines/metabolism
• Extracellular Matrix/metabolism
• Gene Expression Regulation
• Hepatic Stellate Cells/metabolism
• Hepatic Stellate Cells/pathology
• Hepatitis B/complications
• Hepatitis B/metabolism
• Hepatitis C/complications
• Hepatitis C/metabolism
• Humans
• Liver/metabolism
• Liver/pathology
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/etiology
• Liver Cirrhosis/genetics
• Liver Cirrhosis/metabolism
• Liver Cirrhosis/therapy
• Liver Cirrhosis, Alcoholic/etiology
• Liver Cirrhosis, Alcoholic/metabolism
• Non-alcoholic Fatty Liver Disease/complications
• Non-alcoholic Fatty Liver Disease/metabolism
• Risk Factors
• Signal Transduction

• Cirrhosis
• Endotoxemia
• Immune dysfunction

• Adaptive Immunity
• Animals
• Bacterial Infections/immunology
• Bacterial Infections/microbiology
• Bacterial Infections/mortality
• Complement System Proteins/metabolism
• Disease Progression
• End Stage Liver Disease/immunology
• End Stage Liver Disease/mortality
• Humans
• Immunity, Innate
• Inflammation Mediators/metabolism
• Liver Cirrhosis/complications
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/immunology
• Liver Cirrhosis/metabolism
• Liver Cirrhosis/mortality
• Liver Failure, Acute/immunology
• Liver Failure, Acute/mortality
• Macrophages/immunology
• Monocytes/immunology
• Neutrophils/immunology
• Prognosis
• Risk Factors
• Signal Transduction

AIM: To investigate the effect of T helper (Th) 17/T regulatory (Treg) cells on hepatic fibrosis in mice and its possible mechanism.

METHODS: Hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride. Hepatic pathological changes were observed by hematoxylin and eosin staining; the protein levels of interleukin (IL)-6, transforming growth factor (TGF)-β and α-smooth muscle actin (SMA) in liver tissue were determined by Western blotting; and the frequency of Th17 and Treg cells in the liver was estimated by flow cytometry. In addition, hepatic stellate cells were isolated from healthy mouse liver and co-cultured with Th17 or Treg cells. Immunofluorescence staining and Western blotting were performed to determine the change in HSC activation.

RESULTS: In the model group, there were different degrees of fibroplasia, degeneration and necrosis. The protein levels of IL-6, TGF-β and α-SMA in liver tissue were significantly higher than those in the control group at 12 wk (P < 0.05). Compared with the control group, the frequency of Th17 cells in the model group was increased but the frequency of Treg cells decreased gradually. Furthermore, at 4, 8 and 12 wk, there were significant differences in the number of Th17 cells (0.52% ± 0.16%, 1.46% ± 0.24%, and 2.60% ± 0.41%, respectively, P < 0.05) and Treg cells (2.99% ± 0.40%, 2.16% ± 0.50%, and 1.49% ± 0.34%, respectively, P < 0.05). In vitro, Th17 cells promoted, whereas Treg cells inhibited the expression of α-SMA, both in a dose-dependent manner, compared with the control group.

CONCLUSION: Th17/Treg imbalance exists in mice with liver fibrosis, which potentially promotes liver fibrosis via HSC activation.

• T helper 17 cell
• Treg cell
• Carbon tetrachloride
• Hepatic fibrosis
• Hepatic stellate cell

• Actins/metabolism
• Animals
• Carbon Tetrachloride/toxicity
• Flow Cytometry
• Hepatic Stellate Cells/cytology
• Interleukin-6/metabolism
• Liver/metabolism
• Liver/pathology
• Liver Cirrhosis/chemically induced
• Liver Cirrhosis/pathology
• Male
• Mice
• Mice, Inbred C57BL
• Microscopy, Fluorescence
• T-Lymphocytes, Regulatory/cytology
• Th17 Cells/cytology
• Transforming Growth Factor beta/metabolism