The interleukin-17 pathway is involved in human alcoholic liver disease # †

Lemmers, Arnaud; Moreno, Christophe; Gustot, Thierry; Maréchal, Raphaël; Degré, Delphine; Demetter, Pieter; Nadaï, Patricia de; Geerts, Albert; Quertinmont, Eric; Vercruysse, Vincent; Moine, Olivier Le; Devière, Jacques

doi:10.1002/hep.22680

Cited by 346 publications

(348 citation statements)

References 51 publications

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“…We F: female; M: male; n: number of subjects; SD: standard deviation. also confirmed recent findings (Lemmers et al 2009) showing increased IL-17A hepatic levels and Th17 cell numbers associated with the increased severity of liver lesions in patients with alcoholic hepatic disease. Notably, we demonstrated here that serum/liver IL-17A concentrations are very high in patients with autoimmune hepatitis, in accordance with the current data, showing Th17 cells as playing a critical role in autoimmunity (Wong et al 2008).…”

Section: Discussionsupporting

confidence: 91%

“…The balance between the Treg and Th1 responses to HBV/HCV may determine the outcome of immunoprotection or immunopathology (Fainboim et al 2007). Recent studies have suggested that IL-17A/Th17 cells might also participate in the immunopathogenesis of chronic HBV infection (Zhang et al 2010) and alcoholic liver disease (Lemmers et al 2009). Therefore, we evaluated the associations among the presence of Helicobacter in the liver, the aetiology and stage of the hepatic disease and the cytokine pattern displayed by the patients.…”

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confidence: 99%

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The presence of Helicobacter pylori in the liver depends on the Th1, Th17 and Treg cytokine profile of the patient

Silva

Rocha

et al. 2011

Mem. Inst. Oswaldo Cruz

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The hypothesis that Helicobactermight be a risk factor for human liver diseases has arisen after the detection of Helicobacter DNA in hepatic tissue of patients with hepatobiliary diseases. Nevertheless, no explanation that justifies the presence of the bacterium in the human liver has been proposed. We evaluated the presence of Helicobacterin the liver of patients with hepatic diseases of different aetiologies. We prospectively evaluated 147 patients (106 with primary hepatic diseases and 41 with hepatic metastatic tumours) and 20 liver donors as controls. Helicobacter species were investigated in the liver by culture and specific 16S rDNA nested-polymerase chain reaction followed by sequencing. Serum and hepatic levels of representative cytokines of T regulatory cell, T helper (Th)1 and Th17 cell lineages were determined using enzyme linked immunosorbent assay. The data were evaluated using logistic models. Detection of Helicobacter pylori DNA in the liver was independently associated with hepatitis B virus/hepatitis C virus, pancreatic carcinoma and a cytokine pattern characterised by high interleukin (IL)-10, low/absent interferon-γ and decreased IL-17A concentrations (p < 10-3). The bacterial DNA was never detected in the liver of patients with alcoholic cirrhosis and autoimmune hepatitis that are associated with Th1/Th17 polarisation. H. pylori may be observed in the liver of patients with certain hepatic and pancreatic diseases, but this might depend on the patient cytokine profile

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

The presence of Helicobacter pylori in the liver depends on the Th1, Th17 and Treg cytokine profile of the patient

Silva

Rocha

et al. 2011

Mem. Inst. Oswaldo Cruz

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“…HSCs that express multiple receptors are the primary targets of fibrogenic stimuli in the diseased liver. Among these, IL-17RA is the newly discovered receptor expressed in HSC-mediated alcoholic liver fibrosis (24). We also demonstrated that HSCs from C57BL/6 mice constitutively express IL-17RA (Supplemental Fig.…”

Section: Discussionmentioning

confidence: 59%

IL-17A Plays a Critical Role in the Pathogenesis of Liver Fibrosis through Hepatic Stellate Cell Activation

Tan

Qian

Jiang

et al. 2013

The Journal of Immunology

272

208

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Liver fibrosis is a severe, life-threatening clinical condition resulting from nonresolving hepatitis of different origins. IL-17A is critical in inflammation, but its relation to liver fibrosis remains elusive. We find increased IL-17A expression in fibrotic livers from HBV-infected patients undergoing partial hepatectomy because of cirrhosis-related early-stage hepatocellular carcinoma in comparison with control nonfibrotic livers from uninfected patients with hepatic hemangioma. In fibrotic livers, IL-17A immunoreactivity localizes to the inflammatory infiltrate. In experimental carbon tetrachloride–induced liver fibrosis of IL-17RA–deficient mice, we observe reduced neutrophil influx, proinflammatory cytokines, hepatocellular necrosis, inflammation, and fibrosis as compared with control C57BL/6 mice. IL-17A is produced by neutrophils and T lymphocytes expressing the Th17 lineage–specific transcription factor Retinoic acid receptor–related orphan receptor γt. Furthermore, hepatic stellate cells (HSCs) isolated from naive C57BL/6 mice respond to IL-17A with increased IL-6, α-smooth muscle actin, collagen, and TGF-β mRNA expression, suggesting an IL-17A–driven fibrotic process. Pharmacologic ERK1/2 or p38 inhibition significantly attenuated IL-17A–induced HSC activation and collagen expression. In conclusion, IL-17A+ Retinoic acid receptor–related orphan receptor γt+ neutrophils and T cells are recruited into the injured liver driving a chronic, fibrotic hepatitis. IL-17A–dependent HSC activation may be critical for liver fibrosis. Thus, blockade of IL-17A could potentially benefit patients with chronic hepatitis and liver fibrosis.

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“…Two different immunohistochemical techniques were used (19,20) to identify Tbet, GATA3, FOX-P3 and IL-17.…”

Section: Methodsmentioning

confidence: 99%

Th-17 cells infiltrate the liver in human biliary atresia and are related to surgical outcome

Hill

Quaglia

Hussain

et al. 2015

Journal of Pediatric Surgery

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The interleukin-17 pathway is involved in human alcoholic liver disease # †

Cited by 346 publications

References 51 publications

The presence of Helicobacter pylori in the liver depends on the Th1, Th17 and Treg cytokine profile of the patient

The presence of Helicobacter pylori in the liver depends on the Th1, Th17 and Treg cytokine profile of the patient

IL-17A Plays a Critical Role in the Pathogenesis of Liver Fibrosis through Hepatic Stellate Cell Activation

Th-17 cells infiltrate the liver in human biliary atresia and are related to surgical outcome

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