Gut‐derived lymphocyte recruitment to liver and induce liver injury in non‐alcoholic fatty liver disease mouse model

Ying, Haoqiang; Zhang, Henghui; Li, Jing; Xu, Cong; Chen, Yanhui; He, Gaixia; Chi, Yujing; Liu, Yulan

doi:10.1111/jgh.13183

Cited by 30 publications

(32 citation statements)

References 24 publications

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“…30,31 Meanwhile, improved adipose tissue inflammation was also found in B cell depletion mice using anti-CD20 antibody, compared with control mice. 18,37 Using adoptive transfer of MAT B cells and near-infrared scanning in vivo as well as transwell assay, we showed that B cells within inflamed MAT that migrated to the liver increased, promoting the inflammation of hepatocytes. A, Aminotransferase of the culture supernatant in the co-culture system of primary hepatocytes and MAT B cells, either from ND-or HFD-fed mice.…”

Section: Discussionmentioning

confidence: 94%

Mesenteric adipose tissue B lymphocytes promote local and hepatic inflammation in non‐alcoholic fatty liver disease mice

Tan

et al. 2019

J Cellular Molecular Medi

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Mesenteric adipose tissue (MAT) inflammation is associated with non‐alcoholic fatty liver disease (NAFLD), and immune cells play pivotal roles in the inflammation of adipose tissue. Here, we investigated the roles of MAT B lymphocytes in NAFLD. Mice fed with high‐fat diet (HFD) and normal diet (ND) were killed in time gradients (4, 8 and 12 weeks). Compared with ND‐fed mice, intra‐hepatic CD45 + CD19 + B lymphocytes increased after 4 weeks ( P < 0.01) of HFD feeding, and lasted until the 12th week, infiltrated earlier than CD45 + CD3 + T lymphocytes and CD45 + F4/80 + macrophages. The mRNA expression of tumour necrosis factor (TNF)‐α, interleukin (IL)‐6 and monocyte chemotactic protein (MCP)‐1 decreased in MAT of B null HFD‐fed mice compared to that in wild‐type HFD‐fed mice, along with lesser macrophages. Mesenteric adipose tissue B cells from HFD‐fed mice promoted macrophage differentiation to type‐Ι macrophages and expression of pro‐inflammatory cytokines in vitro. Macrophages pre‐treated with MAT B cells from HFD‐fed mice showed elevated mRNA expression of IL‐6 and TNF‐α and declined IL‐10 levels in adipocytes compared to ND MAT B cell pre‐treated macrophages. Besides, internal near‐infrared scanning and external transwell assay showed that HFD MAT B cells migrated to the liver more than ND MAT B cells. High‐fat diet MAT B cells induced higher MCP‐1 and lower IL‐10 expression in primary hepatocytes compared to ND MAT B cells in co‐culture experiment. These data indicate that B lymphocytes infiltrate early in MAT during the development of NAFLD, which may not only promote MAT inflammation by regulating macrophages but also migrate to the liver and induce hepatocytes inflammation.

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Section: Discussionmentioning

confidence: 94%

Mesenteric adipose tissue B lymphocytes promote local and hepatic inflammation in non‐alcoholic fatty liver disease mice

Tan

et al. 2019

J Cellular Molecular Medi

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“…It is known that the GIT microbiota is a major factor in shifting the host to a metabolically diseased state, and the WD fed groups not surprisingly displayed elevated ALT levels and altered microbial markers, many of which are observed in humans with metabolic syndrome (Ley et al, 2006; Tims et al, 2012; Zened et al, 2012; Marietta et al, 2013; Ubeda et al, 2013). If diet is predominantly shaping the GIT microbiota, undesirable microbial products associated with WD may be translocating to the liver via the portal vein, impacting the liver function (Moore et al, 1991; Ilan, 2012; Hu et al, 2016). This can further induce hepatic tissue injury via activation of the inflammasome and chemokine release, creating a vicious circle of liver dysfunction (Ilan, 2012).…”

Section: Discussionmentioning

confidence: 99%

Impact of birth weight and postnatal diet on the gut microbiota of young adult guinea pigs

Sarr

Dunlop

et al. 2017

PeerJ

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BackgroundThe gastrointestinal tract (GIT) microbiota is essential to metabolic health, and the prevalence of the Western diet (WD) high in fat and sugar is increasing, with evidence highlighting a negative interaction between the GIT and WD, resulting in liver dysfunction. Additionally, an adverse in utero environment such as placental insufficiency resulting in low birth weight (LBW) offspring, contributes to an increased risk of metabolic diseases such as fatty liver infiltration and liver dysfunction in later life. We sought to understand the potential interactive effects of exposure to a WD upon growing LBW offspring. We postulated that LBW offspring when challenged with a poor postnatal diet, would display an altered microbiota and more severe liver metabolic dysfunction.MethodsThe fecal microbiota of normal birth weight (NBW) and LBW young guinea pig offspring, weaned onto either a control diet (CD) or WD was determined with 16S rRNA gene next generation sequencing at young adulthood following the early rapid growth phase after weaning. A liver blood chemistry profile was also performed.ResultsThe life-long consumption of WD following weaning into young adulthood resulted in increased total cholesterol, triglycerides and alanine aminotransferase levels in association with an altered GIT microbiota when compared to offspring consuming CD. Neither birth weight nor sex were associated with any significant changes in microbiota alpha diversity, by measuring the Shannon’s diversity index. One hundred forty-eight operational taxonomic units were statistically distinct between the diet groups, independent of birth weight. In the WD group, significant decreases were detected in Barnesiella, Methanobrevibacter smithii and relatives of Oscillospira guillermondii, while Butyricimonas and Bacteroides spp. were increased.DiscussionThese results describe the GIT microbiota in a guinea pig model of LBW and WD associated metabolic syndrome and highlight several WD specific GIT alterations associated with human metabolic disease.

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“…An important element to consider is the site specificity of lymphocytes in NAFLD, as shown in an experimental study where it was observed that the cells infiltrating the liver were labeled lymphocytes that migrated predominantly from mesenteric lymph nodes (MLN) than from spleen, bone marrow, or thymus (63), suggesting that the gut is the primary source of cellular elements involved in NAFLD pathogenesis, which is in turn affected by the microbiota (64, 65). …”

Section: The Role Of Cellular Immune Imbalances In Nafldmentioning

confidence: 99%

Immune Imbalances in Non-Alcoholic Fatty Liver Disease: From General Biomarkers and Neutrophils to Interleukin-17 Axis Activation and New Therapeutic Targets

Paquissi

2016

Front. Immunol.

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Non-alcoholic fatty liver disease (NAFLD) is an increasing problem worldwide and is associated with negative outcomes such as cirrhosis, hepatocellular carcinoma, insulin resistance, diabetes, and cardiovascular events. Current evidence shows that the immune response has an important participation driving the initiation, maintenance, and progression of the disease. So, various immune imbalances, from cellular to cytokines levels, have been studied, either for better compression of the disease pathophysiology or as biomarkers for severity assessment and outcome prediction. In this article, we performed a thorough review of studies that evaluated the role of inflammatory/immune imbalances in the NAFLD. At the cellular level, we gave special focus on the imbalance between neutrophils and lymphocytes counts (the neutrophil-to-lymphocyte ratio), and that which occurs between T helper 17 (Th17) and regulatory T cells as emerging biomarkers. By extension, we reviewed the reflection of these imbalances at the molecular level through pro-inflammatory cytokines including those involved in Th17 differentiation (IL-6, IL-21, IL-23, and transforming growth factor-beta), and those released by Th17 cells (IL-17A, IL-17F, IL-21, and IL-22). We gave particular attention to the role of IL-17, either produced by Th17 cells or neutrophils, in fibrogenesis and steatohepatitis. Finally, we reviewed the potential of these pathways as new therapeutic targets in NAFLD.

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Gut‐derived lymphocyte recruitment to liver and induce liver injury in non‐alcoholic fatty liver disease mouse model

Abstract: Gut-derived lymphocytes from NAFLD mice could migrate to the liver and induce liver injury and hepatic CD4(+) T and CD8(+) T cells activation. The migration was associated with the upregulation of CCL5 in the liver.

Cited by 30 publications

References 24 publications

Mesenteric adipose tissue B lymphocytes promote local and hepatic inflammation in non‐alcoholic fatty liver disease mice

Mesenteric adipose tissue B lymphocytes promote local and hepatic inflammation in non‐alcoholic fatty liver disease mice

Impact of birth weight and postnatal diet on the gut microbiota of young adult guinea pigs

Immune Imbalances in Non-Alcoholic Fatty Liver Disease: From General Biomarkers and Neutrophils to Interleukin-17 Axis Activation and New Therapeutic Targets

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