Impaired CCR9/CCL25 signalling induced by inefficient dendritic cells contributes to intestinal immune imbalance in nonalcoholic steatohepatitis

Gao, Wei; Wang, Yufen; Bi, Jian; Chen, Xiuli; Li, Na; Wang, Kunjie; Tang, Haiying; Mao, Jingsong

doi:10.1016/j.bbrc.2020.12.007

Cited by 12 publications

(4 citation statements)

References 22 publications

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“…GSEA further confirmed the changes in the immune system of liver tissue after BS and found that multiple immune system-related pathways were activated after BS. It turned out that the B cell receptor signaling pathway, T cell receptor signaling pathway, NOD-like receptor signaling pathway, and natural killer cell-mediated cytotoxicity contributed to the occurrence and development of NAFLD/NASH and were involved in the inflammatory response and fibrosis of the liver [41][42][43][44]. There is increasing evidence that innate and adaptive immunities are driving forces in the process of liver inflammation and fibrosis [22,45].…”

Section: Discussionmentioning

confidence: 99%

Screening of Biomarkers in Liver Tissue after Bariatric Surgery Based on WGCNA and SVM-RFE Algorithms

et al. 2023

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As the most common chronic liver disease around the world, nonalcoholic fatty liver disease (NAFLD) has a close connection with obesity, diabetes, and metabolic syndrome. Bariatric surgery (BS) is considered to be the most effective treatment for NAFLD. However, the regulatory mechanism of hepatic lipid metabolism after BS remains poorly elucidated. By analyzing two transcriptome datasets regarding liver tissues after BS, namely, GSE83452 and GSE106737, we acquired 110 differentially expressed genes (DEGs). By further analysis of DEGs in terms of the weighted gene coexpression network analysis (WGCNA) and support vector machine-recursive feature elimination (SVM-RFE) algorithms, we identified four crucial genes participating in the regulation of hepatic lipid metabolism: SRGN, THEMIS2, SGK1, and FPR3. In addition, the results of gene set enrichment analysis (GSEA) showed that BS can activate immune-related regulatory pathways and change immune cell infiltration levels. Finally, through cellular level studies, we found that the silencing of SRGN affects the expression of SREBP-1, SIRT1, and FAS during adipogenesis in the liver and the formation of lipid droplets in the liver. In summary, the immune system in the liver is activated after BS, and SRGN participates in the regulation of hepatic lipid metabolism.

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Section: Discussionmentioning

confidence: 99%

Screening of Biomarkers in Liver Tissue after Bariatric Surgery Based on WGCNA and SVM-RFE Algorithms

et al. 2023

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“…23,25,26 More importantly, it is consistent with our results that during liver injury, peripherally-derived liver macrophages are mainly recruited from circulation through CCL2/CCR2, 27 and gut-derived macrophage recruitment in the liver depends on intestinal-specific CCR9/CCL25 and α4β7/VAP-1/MAdCAM-1. 28,29 Splenic macrophages promote hepatic macrophage secretion of CCL2, which in turn facilitates monocyte recruitment and the establishment of an M1-dominant hepatic macrophage phenotype. 30 CCR9 and its ligand CCL25 contribute to the progression of nonalcoholic steatohepatitis and carcinogenesis in humans and mice.…”

Section: Discussionmentioning

confidence: 99%

MiR-155-5p-SOCS1/JAK1/STAT1 participates in hepatic lymphangiogenesis in liver fibrosis and cirrhosis by regulating M1 macrophage polarization

Liu

Chen

et al. 2023

Hum Exp Toxicol

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Background The role and underlying mechanism of liver macrophages and their derived miR-155-5p in hepatic lymphangiogenesis in liver fibrosis remain unclear. Here, we investigated the mechanism by which macrophages and miR-155-5p were involved in lymphangiogenesis during liver fibrosis and cirrhosis. Methods In vivo, hepatic lymphatic vessel expansion was evaluated; the liver macrophage subsets, proportion of peripherally-derived macrophages and expressions of CCL25, MCP-1, VAP-1 and MAdCAM-1 were documented; and miR-155-5p in the peripheral blood and liver was detected. In vitro, macrophages with miR-155-5p overexpression and inhibition were used to clarify the effect of miR-155-5p on regulation of macrophage polarization and the possible signalling pathway. Results Hepatic lymphangiogenesis was observed in mice with liver fibrosis and cirrhosis challenged with carbon tetrachloride (CCl4). In the liver, the number of M1 macrophages was associated with lymphangiogenesis and the degree of fibrosis. The liver recruitment of peripherally-derived macrophages occurred during liver fibrosis. The levels of miR-155-5p in the liver and peripheral blood gradually increased with aggravation of liver fibrosis. In vitro, SOCS1, a target of miR-155-5p, regulated macrophage polarization into the M1 phenotype through the JAK1/STAT1 pathway. Conclusion MiR-155-5p-SOCS1/JAK1/STAT1 pathway participates in hepatic lymphangiogenesis in mice with liver fibrosis and cirrhosis induced by CCl4 by regulating the polarization of macrophages into the M1 phenotype.

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“…Conversely, a reduced proportion of Th17 cells within CD4 + T cells was detected in the small intestinal lamina propria of mice fed an HFD for 10 weeks compared to those fed a normal diet ( 110 ). Similarly, in the MLNs, a lower Th17 cell proportion of CD4 + T cells was found in the MCD diet-induced NASH mouse model compared to mice fed a normal diet ( 111 ). To these controverted findings, we can add that HFD-fed mice present increased IL-17-producing γδ T cells in the small and large intestinal lamina propria ( 106 ).…”

Section: Gut Mucosal Immunity In Nafldmentioning

confidence: 92%

“…In HFD-fed mice, decreased levels of FOXP3 + Treg cells in the intestinal lamina propria ( 106 ) and a reduced proportion of CD4 + /FOXP3 + cells in the MLNs compared to mice fed a normal diet ( 107 ) have been reported. In contrast, the MCD diet-induced NASH mouse model presented an increased FOXP3 + Treg cell proportion of CD4 + T cells in the MLNs compared to mice fed a normal diet ( 111 ). A therapeutic strategy based on oral anti-CD3 mAbs to elicit Treg induction has been explored in NASH treatment ( 116 ).…”

Section: Gut Mucosal Immunity In Nafldmentioning

confidence: 96%

The immune response as a therapeutic target in non-alcoholic fatty liver disease

et al. 2022

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Non-alcoholic fatty liver disease (NAFLD) is a complex and heterogeneous disorder considered a liver-damaging manifestation of metabolic syndrome. Its prevalence has increased in the last decades due to modern-day lifestyle factors associated with overweight and obesity, making it a relevant public health problem worldwide. The clinical progression of NAFLD is associated with advanced forms of liver injury such as fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). As such, diverse pharmacological strategies have been implemented over the last few years, principally focused on metabolic pathways involved in NAFLD progression. However, a variable response rate has been observed in NAFLD patients, which is explained by the interindividual heterogeneity of susceptibility to liver damage. In this scenario, it is necessary to search for different therapeutic approaches. It is worth noting that chronic low-grade inflammation constitutes a central mechanism in the pathogenesis and progression of NAFLD, associated with abnormal composition of the intestinal microbiota, increased lymphocyte activation in the intestine and immune effector mechanisms in liver. This review aims to discuss the current knowledge about the role of the immune response in NAFLD development. We have focused mainly on the impact of altered gut-liver-microbiota axis communication on immune cell activation in the intestinal mucosa and the role of subsequent lymphocyte homing to the liver in NAFLD development. We further discuss novel clinical trials that addressed the control of the liver and intestinal immune response to complement current NAFLD therapies.

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Impaired CCR9/CCL25 signalling induced by inefficient dendritic cells contributes to intestinal immune imbalance in nonalcoholic steatohepatitis

Cited by 12 publications

References 22 publications

Screening of Biomarkers in Liver Tissue after Bariatric Surgery Based on WGCNA and SVM-RFE Algorithms

Screening of Biomarkers in Liver Tissue after Bariatric Surgery Based on WGCNA and SVM-RFE Algorithms

MiR-155-5p-SOCS1/JAK1/STAT1 participates in hepatic lymphangiogenesis in liver fibrosis and cirrhosis by regulating M1 macrophage polarization

The immune response as a therapeutic target in non-alcoholic fatty liver disease

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