Myeloid cells in alcoholic liver diseases: Mechanism and prospect

Xu, Wentao; Wu, Miaomiao; Chen, Bangjie; Wang, Hua

doi:10.3389/fimmu.2022.971346

Cited by 3 publications

(2 citation statements)

References 56 publications

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“…During hepatic fibrosis, DCs proliferate and undergo phenotypic changes. They stimulate adjacent T cells and natural killer(NK) cells through TNF-α, and up-regulate intercellular adhesion molecule-1 and CD40 expression of HSCs, thus, promoting the HSCs proliferation and activation ( 30 , 31 ). DCs also aggravate liver inflammation by inhibiting infiltration of Treg cells and activating TLRs to produce a large number of cytokines ( 32 ).…”

Section: Dendritic Cellsmentioning

confidence: 99%

Ongoing involvers and promising therapeutic targets of hepatic fibrosis: The hepatic immune microenvironment

et al. 2023

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Hepatic fibrosis is often secondary to chronic inflammatory liver injury. During the development of hepatic fibrosis, the damaged hepatocytes and activated hepatic stellate cells (HSCs) caused by the pathogenic injury could secrete a variety of cytokines and chemokines, which will chemotactic innate and adaptive immune cells of liver tissue and peripheral circulation infiltrating into the injury site, mediating the immune response against injury and promoting tissue reparation. However, the continuous release of persistent injurious stimulus-induced inflammatory cytokines will promote HSCs-mediated fibrous tissue hyperproliferation and excessive repair, which will cause hepatic fibrosis development and progression to cirrhosis even liver cancer. And the activated HSCs can secrete various cytokines and chemokines, which directly interact with immune cells and actively participate in liver disease progression. Therefore, analyzing the changes in local immune homeostasis caused by immune response under different pathological states will greatly enrich our understanding of liver diseases’ reversal, chronicity, progression, and even deterioration of liver cancer. In this review, we summarized the critical components of the hepatic immune microenvironment (HIME), different sub-type immune cells, and their released cytokines, according to their effect on the development of progression of hepatic fibrosis. And we also reviewed and analyzed the specific changes and the related mechanisms of the immune microenvironment in different chronic liver diseases.Moreover, we retrospectively analyzed whether the progression of hepatic fibrosis could be alleviated by modulating the HIME.We aimed to elucidate the pathogenesis of hepatic fibrosis and provide the possibility for exploring the therapeutic targets for hepatic fibrosis.

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Section: Dendritic Cellsmentioning

confidence: 99%

Ongoing involvers and promising therapeutic targets of hepatic fibrosis: The hepatic immune microenvironment

et al. 2023

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“…Myeloid cells differentiate from bone marrow precursors to become mature circulating granulocytes (neutrophils, eosinophils, and basophils) and monocytes. These cells often function as a first line of defense against infection but can also precipitate end organ injury or drive resolution depending on the specific disease context ( 14 ). Such myeloid cells have been associated with the pathophysiology of ARLD.…”

Section: Introductionmentioning

confidence: 99%

Circulating myeloid populations have prognostic utility in alcohol-related liver disease

Khan,

Salman,

Harford

et al. 2024

Front. Immunol.

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IntroductionAlcohol-related liver disease (ARLD) accounts for over one third of all deaths from liver conditions, and mortality from alcohol-related liver disease has increased nearly five-fold over the last 30 years. Severe alcohol-related hepatitis almost always occurs in patients with a background of chronic liver disease with extensive fibrosis or cirrhosis, can precipitate ‘acute on chronic’ liver failure and has a high short-term mortality. Patients with alcohol-related liver disease have impaired immune responses, and increased susceptibility to infections, thus prompt diagnosis of infection and careful patient management is required. The identification of early and non-invasive diagnostic and prognostic biomarkers in ARLD remains an unresolved challenge. Easily calculated predictors of infection and mortality are required for use in patients who often exhibit variable symptoms and disease severity and may not always present in a specialized gastroenterology unit.MethodsWe have used a simple haematological analyser to rapidly measure circulating myeloid cell parameters across the ARLD spectrum.Results and DiscussionWe demonstrate for the first time that immature granulocyte (IG) counts correlate with markers of disease severity, and our data suggests that elevated counts are associated with increased short-term mortality and risk of infection. Other myeloid populations such as eosinophils and basophils also show promise. Thus IG count has the potential to serve alongside established markers such as neutrophil: lymphocyte ratio as a simply calculated predictor of mortality and risk of infectious complications in patients with alcohol-related hepatitis. This would allow identification of patients who may require more intensive management.

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Macrophage-expressed SRA ameliorates alcohol-induced liver injury by suppressing S-glutathionylation of Notch1 via recruiting thioredoxin

Li,

Luo,

Zhu

et al. 2023

Journal of Leukocyte Biology

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Scavenger receptor A (SRA) is preferentially expressed in macrophages and implicated as a multifunctional pattern recognition receptor for innate immunity. Hepatic macrophages play a primary role in the pathogenesis of alcoholic liver disease (ALD). Herein, we observed that SRA expression was significantly increased in the liver tissues of mice with alcohol-related liver injury. SRA-deficient (SRA−/−) mice developed more severe alcohol-induced liver disease than wild-type (WT) mice. Enhanced liver inflammation existed in alcohol-challenged SRA−/− mice and was associated with increased Notch activation in hepatic macrophages compared with WT controls. Mechanistically, SRA directly bound with Notch1 and suppressed its S-glutathionylation, thereby inhibiting Notch pathway activation. Further, we determined the SRA interacted with thioredoxin-1 (Trx-1), a redox-active protein. SRA inhibited Trx-1 dimerization and facilitated the interaction of Trx-1 with Notch1. Application of a Trx-1-specific inhibitory agent during macrophage stimulation abolished SRA-mediated regulation of the Notch pathway and its downstream targets. In summary, our study revealed that SRA plays a critical role in macrophage inflammatory response by targeting Notch1 for its glutathionylation. SRA-mediated negative regulation of Notch activation might serve as a novel therapeutic strategy for alcohol-induced liver injury.

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Myeloid cells in alcoholic liver diseases: Mechanism and prospect

Cited by 3 publications

References 56 publications

Ongoing involvers and promising therapeutic targets of hepatic fibrosis: The hepatic immune microenvironment

Ongoing involvers and promising therapeutic targets of hepatic fibrosis: The hepatic immune microenvironment

Circulating myeloid populations have prognostic utility in alcohol-related liver disease

Macrophage-expressed SRA ameliorates alcohol-induced liver injury by suppressing S-glutathionylation of Notch1 via recruiting thioredoxin

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