Crucial role of T cells in NAFLD-related disease: A review and prospect

Mao, Tianyu; Yang, Rui; Luo, Yi; He, Kai

doi:10.3389/fendo.2022.1051076

Cited by 13 publications

(5 citation statements)

References 206 publications

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“…In our research, it was discovered that this particular molecule exhibited a strong positive correlation with the infiltration of activated CD4 T cells in NAFLD. Earlier research had validated that stimulated CD4 T cell types, like Th1 and Th17, possess the ability to release diverse cytokines, including IFN-gand IL-17, thereby enhancing liver inflammation (47)(48)(49). Hence, we hypothesized that this compound might have a crucial function in the progression of SS to NASH.…”

Section: Discussionmentioning

confidence: 96%

Expression of immune related genes and possible regulatory mechanisms in different stages of non-alcoholic fatty liver disease

He,

Guan,

Zhao

et al. 2024

Front. Immunol.

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BackgroundNon-alcoholic fatty liver disease (NAFLD), which includes simple steatosis (SS) and non-alcoholic steatohepatitis (NASH), is a significant contributor to liver disease on a global scale. The change of immunity-related genes (IRGs) expression level leads to different immune infiltrations. However, the expression of IRGs and possible regulatory mechanisms involved in NAFLD remain unclear. The objective of our research is to investigate crucial genes linked to the development of NAFLD and the transition from SS to NASH.MethodsDataset GSE89632, which includes healthy controls, SS patients, and NASH patients, was obtained using the GEO database. To examine the correlation between sets of genes and clinical characteristics, we employed weighted gene co-expression network analysis (WGCNA) and differential expression analysis. Hub genes were extracted using a network of protein-protein interactions (PPI) and three different machine learning algorithms. To validate the findings, another dataset that is publicly accessible and mice that were subjected to a high-fat diet (HFD) or MCD diet were utilized. Furthermore, the ESTIMATE algorithm and ssGSEA were employed to investigate the immune landscape in the normal versus SS group and SS versus NASH group, additionally, the relationship between immune infiltration and the expression of hub genes was also examined.ResultsA total of 28 immune related key genes were selected. Most of these genes expressed reverse patterns in the initial and progressive stages of NAFLD. GO and KEGG analyses showed that they were focused on the cytokine related pathways and immune cell activation and chemotaxis. After screening by various algorithms, we obtained two hub genes, including JUN and CCL20. Validation of these findings was confirmed by analyzing gene expression patterns in both the validation dataset and the mouse model. Ultimately, two hub genes were discovered to have a significant correlation with the infiltration of immune cells.ConclusionWe proposed that there were dynamic changes in the expression levels of IRGs in different stages of NAFLD disease, which led to different immune landscapes in SS and NASH. The findings of our research could serve as a guide for the accurate management of various phases of NAFLD.

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Section: Discussionmentioning

confidence: 96%

Expression of immune related genes and possible regulatory mechanisms in different stages of non-alcoholic fatty liver disease

He,

Guan,

Zhao

et al. 2024

Front. Immunol.

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“… 42 Furthermore, CD8+ T cells have been shown to promote MASLD progression by inducing hepatocyte death and fibrosis. 43 …”

Section: Discussionmentioning

confidence: 99%

Multiscale integrative analyses unveil immune-related diagnostic signature for the progression of MASLD

Bai,

Zhu,

et al. 2023

Hepatology Communications

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Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease prevalent worldwide, with an increasing incidence associated with obesity, diabetes, and metabolic syndrome. The progression of MASLD to metabolic dysfunction–associated steatohepatitis (MASH) poses a pressing health concern, highlighting the significance of accurately identifying MASLD and its progression to MASH as a primary challenge in the field. In this study, a systematic integration of 66 immune cell types was conducted. Comprehensive analyses were performed on bulk, single-cell RNA-Seq, and clinical data to investigate the immune cell types implicated in MASLD progression thoroughly. Multiple approaches, including immune infiltration, gene expression trend analysis, weighted gene coexpression network analysis, and 4 machine learning algorithms, were used to examine the dynamic changes in genes and immune cells during MASLD progression. C-X-C motif chemokine receptor 4 and dedicator of cytokinesis 8 have been identified as potential diagnostic biomarkers for MASLD progression. Furthermore, cell communication analysis at the single-cell level revealed that the involvement of C-X-C motif chemokine receptor 4 and dedicator of cytokinesis 8 in MASLD progression is mediated through their influence on T cells. Overall, our study identified vital immune cells and a 2-gene diagnostic signature for the progression of MASLD, providing a new perspective on the diagnosis and immune-related molecular mechanisms of MASLD. These findings have important implications for developing innovative diagnostic tools and therapies for MASLD.

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“…On the other hand, the role of ligands of PD-1 and PD-L1 in MASLD and NASH is better understood. During the chronic lipotoxicity-mediated injury of hepatocytes, the activation of KCs is mediated by TLR receptors [128]. KCs represent the first line of defense and, when activated, they release pro-inflammatory factors, such as TNF-α, IL-1β, IL-6, IL-12, and IL-18 [21].…”

Section: Pro-and Anti-inflammatory Effects Of Pd-1/pd-l1 Axis In Masl...mentioning

confidence: 99%

The PD-1/PD-L1 Axis in the Biology of MASLD

Pipitone,

Lupo,

Zito

et al. 2024

IJMS

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Metabolic Dysfunction-Associated Steatotic Liver (MASL), previously named nonalcoholic fatty liver (NAFL), is a multifactorial disease in which metabolic, genetic, and environmental risk factors play a predominant role. Obesity and type 2 diabetes act as triggers of the inflammatory response, which contributes to the progression of MASL to Metabolic Dysfunction-Associated Steatohepatitis and the development of hepatocellular carcinoma. In the liver, several parenchymal, nonparenchymal, and immune cells maintain immunological homeostasis, and different regulatory pathways balance the activation of the innate and adaptative immune system. PD-1/PD-L1 signaling acts, in the maintenance of the balance between the immune responses and the tissue immune homeostasis, promoting self-tolerance through the modulation of activated T cells. Recently, PD-1 has received much attention for its roles in inducing an exhausted T cells phenotype, promoting the tumor escape from immune responses. Indeed, in MASLD, the excessive fat accumulation dysregulates the immune system, increasing cytotoxic lymphocytes and decreasing their cytolytic activity. In this context, T cells exacerbate liver damage and promote tumor progression. The aim of this review is to illustrate the main pathogenetic mechanisms by which the immune system promotes the progression of MASLD and the transition to HCC, as well as to discuss the possible therapeutic applications of PD-1/PD-L1 target therapy to activate T cells and reinvigorate immune surveillance against cancer.

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Crucial role of T cells in NAFLD-related disease: A review and prospect

Cited by 13 publications

References 206 publications

Expression of immune related genes and possible regulatory mechanisms in different stages of non-alcoholic fatty liver disease

Expression of immune related genes and possible regulatory mechanisms in different stages of non-alcoholic fatty liver disease

Multiscale integrative analyses unveil immune-related diagnostic signature for the progression of MASLD

The PD-1/PD-L1 Axis in the Biology of MASLD

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