The Role of Innate Cells Is Coupled to a Th1-Polarized Immune Response in Pediatric Nonalcoholic Steatohepatitis

Solari, Nazarena E. Ferreyra; Inzaugarat, María Eugenia; Baz, Plácida; Matteo, Elena De; Lezama, Carol; Galoppo, Marcela; Galoppo, Cristina; Cherñavsky, Alejandra Claudia

doi:10.1007/s10875-011-9635-2

Cited by 60 publications

(56 citation statements)

References 41 publications

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“…Animal experiments indicated that adoptive transfer of Treg cells into mice could alleviate HFD-induced steatohepatitis 38, 47 . Cytokines such as IFN-γ and IL-17 from Th1 and Th17 cells can promote the release of IL-6 and TNF-α, which aggravate liver insulin resistance and steatohepatitis 46, 48 . Previous work showed that intrahepatic IL-17 was significantly elevated in NASH patients.…”

Section: Discussionmentioning

confidence: 99%

Total fecal microbiota transplantation alleviates high-fat diet-induced steatohepatitis in mice via beneficial regulation of gut microbiota

Zhou

Pan

Shen

et al. 2017

Sci Rep

285

219

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Non-alcoholic steatohepatitis (NASH) is an epidemic metabolic disease with limited therapeutic strategies. Cumulative data support the pivotal role of gut microbiota in NASH. Here, we investigated the hypothesis regarding whether fecal microbiota transplantation (FMT) is effective in attenuating high-fat diet (HFD)-induced steatohepatitis in mice. Mice were randomized into control, HFD and HFD + FMT groups. After an 8-week HFD, FMT treatment was initiated and carried out for 8 weeks. The gut microbiota structure, butyrate concentrations of the cecal content, liver pathology and intrahepatic lipid and cytokines were examined. Our results showed that after FMT, the gut microbiota disturbance was corrected in HFD-fed mice with elevated abundances of the beneficial bacteria Christensenellaceae and Lactobacillus. FMT also increased butyrate concentrations of the cecal content and the intestinal tight junction protein ZO-1, resulting in relief of endotoxima in HFD-fed mice. Steatohepatitis was alleviated after FMT, as indicated by a significant decrease in intrahepatic lipid accumulation (reduced Oli-red staining, decreased intrahepatic triglyceride and cholesterol), intrahepatic pro-inflammatory cytokines, and the NAS score. Accordingly, intrahepatic IFN-γ and IL-17 were decreased, but Foxp3, IL-4 and IL-22 were increased after FMT intervention. These data indicate that FMT attenuated HFD-induced steatohepatitis in mice via a beneficial effect on the gut microbiota.

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Section: Discussionmentioning

confidence: 99%

Total fecal microbiota transplantation alleviates high-fat diet-induced steatohepatitis in mice via beneficial regulation of gut microbiota

Zhou

Pan

Shen

et al. 2017

Sci Rep

285

219

View full text Add to dashboard Cite

show abstract

“…Gene expression analysis of liver tissue and hepatic inflammatory cells from NASH mice showed that Th1‐, Th2‐, and Th17‐related genes were down‐regulated by ADSC treatment. Helper T‐cell activation skewed to produce Th1 cytokines is pathogenic in steatohepatitis . In particular, Th17 is emerging as an important source of IL‐17 family cytokines and is involved in the hepatic inflammation in NASH .…”

Section: Discussionmentioning

confidence: 99%

Adipose tissue-derived stem cells as a regenerative therapy for a mouse steatohepatitis-induced cirrhosis model

et al. 2013

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Cirrhosis is a chronic liver disease that impairs hepatic function and causes advanced fibrosis. Mesenchymal stem cells have gained recent popularity as a regenerative therapy since they possess immunomodulatory functions. We found that injected adipose tissue‐derived stem cells (ADSCs) reside in the liver. Injection of ADSCs also restores albumin expression in hepatic parenchymal cells and ameliorates fibrosis in a nonalcoholic steatohepatitis model of cirrhosis in mice. Gene expression analysis of the liver identifies up‐ and down‐regulation of genes, indicating regeneration/repair and anti‐inflammatory processes following ADSC injection. ADSC treatment also decreases the number of intrahepatic infiltrating CD11b+ and Gr‐1+ cells and reduces the ratio of CD8+/CD4+ cells in hepatic inflammatory cells. This is consistent with down‐regulation of genes in hepatic inflammatory cells related to antigen presentation and helper T‐cell activation. Conclusion: These results suggest that ADSC therapy is beneficial in cirrhosis, as it can repair and restore the function of the impaired liver. (Hepatology 2013;53:1133–1142)

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“…In addition, cytokines are not only being produced by local sources but also by peripheral blood cells. The presence of an altered phenotype and functionality of circulating immune cells has been speculated to be a distinctive characteristic in NASH patients [76,77] . Innate immune cells have the ability to secrete cyto-kines and to promote influx of inflammatory cells.…”

Section: Immune Cells and Cytokinesmentioning

confidence: 99%

Proteomic and genomic studies of non-alcoholic fatty liver disease - clues in the pathogenesis

Lim

Dillon

Miller

2014

WJG

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Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder that covers wide spectrum of liver pathology. NAFLD is strongly associated with liver inflammation, metabolic hyperlipidaemia and insulin resistance. Frequently, NAFLD has been considered as the hepatic manifestation of metabolic syndrome. The pathophysiology of NAFLD has not been fully elucidated. Some patients can remain in the stage of simple steatosis, which generally is a benign condition; whereas others can develop liver inflammation and progress into non-alcoholic steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. The mechanism behind the progression is still not fully understood. Much ongoing proteomic researches have focused on discovering the unbiased circulating biochemical markers to allow early detection and treatment of NAFLD. Comprehensive genomic studies have also begun to provide new insights into the gene polymorphism to understand patientdisease variations. Therefore, NAFLD is considered a complex and mutifactorial disease phenotype resulting from environmental exposures acting on a susceptible polygenic background. This paper reviewed the current status of proteomic and genomic studies that have contributed to the understanding of NAFLD pathogenesis. For proteomics section, this review highlighted functional proteins that involved in: (1) transportation; (2) metabolic pathway; (3) acute phase reaction; (4) antiinflammatory; (5) extracellular matrix; and (6) immune system. In the genomic studies, this review will discuss genes which involved in: (1) lipolysis; (2) adipokines; and (3) cytokines production. Key words: Non-alcoholic fatty liver disease; Proteomics; Genomics; Metabolic syndrome; Pathophysiology Core tip: Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder in Western populations. NAFLD can occur as a spectrum diseases, from simple steatosis, to non-alcoholic steatohepatitis characterised by hepatocellular injury and inflammation, to cirrhosis and hepatocellular carcinoma. This paper reviewed the current status of proteomic and genomic studies that have contributed to the understanding of NAFLD pathogenesis. This review highlighted several functional proteins and genetic polymoprhisms; particular those involved in insulin resistance, triglycerides metabolism and hepatic inflammation. It is hoped that this review will offer further insights into the pathophysiology of NAFLD.

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The Role of Innate Cells Is Coupled to a Th1-Polarized Immune Response in Pediatric Nonalcoholic Steatohepatitis

Abstract: In sum, the distinctive phenotype and functionality of infiltrating and circulating cells suggest that the role of innate cells is coupled to a Th1-polarized immune response in pediatric NASH.

Cited by 60 publications

References 41 publications

Total fecal microbiota transplantation alleviates high-fat diet-induced steatohepatitis in mice via beneficial regulation of gut microbiota

Total fecal microbiota transplantation alleviates high-fat diet-induced steatohepatitis in mice via beneficial regulation of gut microbiota

Adipose tissue-derived stem cells as a regenerative therapy for a mouse steatohepatitis-induced cirrhosis model

Proteomic and genomic studies of non-alcoholic fatty liver disease - clues in the pathogenesis

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