MAIT cells: a novel therapeutic target for alcoholic liver disease?

Gao, Bin; Ma, Jing; Xiang, Xiaogang

doi:10.1136/gutjnl-2017-315284

Cited by 18 publications

(19 citation statements)

References 14 publications

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“…28 A marked reduction of MAIT cells has been observed in patients with ALD, which may contribute to the increased risk of bacterial infection in these patients. 29,30…”

Section: Key Pointsmentioning

confidence: 99%

Inflammatory pathways in alcoholic steatohepatitis

Gao

Ahmad

Nagy

et al. 2019

Journal of Hepatology

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245

253

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Inflammatory processes are primary contributors to the development and progression of alcoholic steatohepatitis (ASH), with severe alcoholic hepatitis characterised by non-resolving inflammation. Inflammation in the progression of ASH is a complex response to microbial dysbiosis, loss of barrier integrity in the intestine, hepatocellular stress and death, as well as inter-organ crosstalk. Herein, we review the roles of multiple cell types that are involved in inflammation in ASH, including resident macrophages and infiltrating monocytes, as well as other cell types in the innate and adaptive immune system. In response to chronic, heavy alcohol exposure, hepatocytes themselves also contribute to the inflammatory process; hepatocytes express a large number of chemokines and inflammatory mediators and can also release damage-associated molecular patterns during injury and death. These cellular responses are mediated and accompanied by changes in the expression of pro-and anti-inflammatory cytokines and chemokines, as well as by signals which orchestrate the recruitment of immune cells and activation of the inflammatory process. Additional mechanisms for cell-cell and inter-organ communication in ASH are also reviewed, including the roles of extracellular vesicles and microRNAs, as well as inter-organ crosstalk. We highlight the concept that inflammation also plays an important role in promoting liver repair and controlling bacterial infection. Understanding the complex regulatory processes that are disrupted during the progression of ASH will likely lead to better targeted strategies for therapeutic interventions.

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“…28 A marked reduction of MAIT cells has been observed in patients with ALD, which may contribute to the increased risk of bacterial infection in these patients. 29,30…”

Section: Key Pointsmentioning

confidence: 99%

Inflammatory pathways in alcoholic steatohepatitis

Gao

Ahmad

Nagy

et al. 2019

Journal of Hepatology

Self Cite

245

253

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“…An alteration in MAIT cells induced by faecal microbiota is a likely mechanism for the beneficial effects of FMT. 124 Alcohol-sensitive mice were noted to have reduced Bacteroidetes, with increased levels of Actinobacteria and Firmicutes. Alcohol-sensitive mice had 50% less Bacteroides than alcoholresistant mice.…”

Section: Possible Mechanisms Of Action Of Fmtmentioning

confidence: 99%

Microbiome as a therapeutic target in alcohol-related liver disease

Sarin

Pande

Schnabl

2019

Journal of Hepatology

178

142

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Alcohol-related liver disease is associated with significant changes in gut microbial composition. The transmissibility of ethanol-induced liver disease has been demonstrated using faecal microbiota transfer in preclinical models. This technique has also led to improved survival in patients with severe alcoholic hepatitis, suggesting that changes in the composition and function of the gut microbiota are causatively linked to alcohol-related liver disease. A major mechanism by which gut microbiota influence the development of alcohol-related liver disease is through a leaky intestinal barrier. This permits translocation of viable bacteria and microbial products to the liver, where they induce and promote inflammation, as well as contribute to hepatocyte death and the fibrotic response. In addition, gut dysbiosis is associated with changes in the metabolic function of the intestinal microbiota, bile acid composition and circulation, immune dysregulation during onset and progression of alcohol-related liver disease. Findings from preclinical and human studies will be used to demonstrate how alcohol causes intestinal pathology and contributes to alcohol-related liver disease and how the latter is self-perpetuating. Additionally, we summarise the effects of untargeted treatment approaches on the gut microbiota, such as diet, probiotics, antibiotics and faecal microbial transplantation in alcohol-related liver disease. We further discuss how targeted approaches can restore intestinal homeostasis and improve alcohol-related liver disease. These approaches are likely to add to the therapeutic options for alcohol-related liver disease independently or in conjunction with steroids. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.Gut microbiota contributes to the development of alcohol-related liver disease via different mechanisms. The altered gut bacteria in alcoholic hepatitis lead to suppression of the immune system, increase in hepatic inflammation and changes in microbial metabolites.

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“…These studies opened a new direction on the fields of MAIT cells. Bin Gao et al [71] confirmed MAIT cells likely exerted an important role in controlling the bacterial infection though MAIT cells had defects in the frequency and function among ASH patients. He also suggested that there are more aspects to explore.…”

Section: Alcoholic Liver Diseasementioning

confidence: 99%

Mucosal-Associated Invariant T cell in liver diseases

Zhang¹,

Kong²,

Wang³

2020

Int. J. Biol. Sci.

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Mucosal-associated invariant T cells (MAIT cells) are a new population of innate immune cells, which are abundant in the liver and play complex roles in various liver diseases. In this review, we summarize MAIT cells in the liver diseases in recent studies, figure out the role of MAIT cells in various liver disease, including Alcoholic liver disease, Non-alcoholic liver disease, Autoimmune liver diseases, Viral hepatitis and Liver Cancer. Briefly, MAIT cells are involved in anti-bacteria responses in the alcoholic liver diseases. Besides, the activated MAIT cells promote the liver inflammation by secreting inflammatory cytokines and produce regulatory cytokines, which induces anti-inflammatory macrophage polarization. MAIT cells participate in the liver fibrosis via enhancing hepatic stellate cell activation. In viral hepatitis, MAIT cells exhibit a flawed and exhausted phenotype, which results in little effect on controlling the virus and bacteria. In liver cancer, MAIT cells indicate the disease progression and the outcome of therapy. In summary, MAIT cells are attractive biomarkers and therapeutic targets for liver disease.

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MAIT cells: a novel therapeutic target for alcoholic liver disease?

Cited by 18 publications

References 14 publications

Inflammatory pathways in alcoholic steatohepatitis

Inflammatory pathways in alcoholic steatohepatitis

Microbiome as a therapeutic target in alcohol-related liver disease

Mucosal-Associated Invariant T cell in liver diseases

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