Immunopathobiology and therapeutic targets related to cytokines in liver diseases

He, Yong; Hwang, Seonghwan; Ahmed, Yeni Ait; Feng, Dechun; Li, Na; Ribeiro, Marcelle; Lafdil, Fouad; Kisseleva, Tatiana; Szabó, Gyöngyi; Gao, Bin

doi:10.1038/s41423-020-00580-w

Cited by 84 publications

(75 citation statements)

References 308 publications

(410 reference statements)

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“…It is tempting to speculate that the RNF213 variants seen in these patients disrupt NF‐kB signaling and the immune response more severely than previously described variants. This phenomenon may also be relevant to the hepatitis phenotype, as hepatocytes have a TNF‐receptors and may be injured by disrupted NF‐kB signaling (He et al, 2021 ). Skin pathology may also be related to impaired kidney and liver function and accumulating metabolites with cutaneous toxicity; however, neither patient had a GFR sufficient low to disrupt toxin clearance and liver function was preserved in both patients.…”

Section: Discussionmentioning

confidence: 99%

A new syndrome of moyamoya disease, kidney dysplasia, aminotransferase elevation, and skin disease associated with de novo variants in RNF213

Strong

O’Grady

Shih

et al. 2021

American J of Med Genetics Pt A

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Ring‐finger protein 213 (RNF213) encodes a protein of unknown function believed to play a role in cellular metabolism and angiogenesis. Gene variants are associated with susceptibility to moyamoya disease. Here, we describe two children with moyamoya disease who also demonstrated kidney disease, elevated aminotransferases, and recurrent skin lesions found by exome sequencing to have de novo missense variants in RNF213. These cases highlight the ability of RNF213 to cause Mendelian moyamoya disease in addition to acting as a genetic susceptibility locus. The cases also suggest a new, multi‐organ RNF213‐spectrum disease characterized by liver, skin, and kidney pathology in addition to severe moyamoya disease caused by heterozygous, de novo C‐terminal RNF213 missense variants.

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Section: Discussionmentioning

confidence: 99%

A new syndrome of moyamoya disease, kidney dysplasia, aminotransferase elevation, and skin disease associated with de novo variants in RNF213

Strong

O’Grady

Shih

et al. 2021

American J of Med Genetics Pt A

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“…Chronic fat overload induces liver cell death, resulting in the release of danger associated molecular patterns triggering macrophage activation 157 . During chronic liver injury, the increased recruitment of monocyte‐derived macrophages and Kupffer cell populations leads to increased circulating levels of systemic inflammatory markers, including IL‐1, IL‐6 and subfamilies of IL‐20 158 . This process could worsen the CVD risk through endothelial dysfunction, altered vascular tone, raised plaque formation and clotting 159 …”

Section: Nafld and Risk Of Cardiovascular Diseasesmentioning

confidence: 99%

Nonalcoholic fatty liver disease or metabolic dysfunction‐associated fatty liver disease diagnoses and cardiovascular diseases: From epidemiology to drug approaches

Dongiovanni

Paolini

Corsini

et al. 2021

Eur J Clin Investigation

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Background A consensus of experts has proposed to replace the term nonalcoholic fatty liver disease (NAFLD), whose global prevalence is 25%, with metabolic dysfunction‐associated fatty liver disease (MAFLD), to describe more appropriately the liver disease related to metabolic derangements. MAFLD is closely intertwined with type 2 diabetes, obesity, dyslipidaemia, all linked to a rise in the risk of cardiovascular disease (CVDs). Since controversy still stands on whether or not NAFLD/MAFLD raises the odds of CVD, the present review aims to evaluate the impact of NAFLD/MAFLD aetiologies on CV health and the potential correction by dietary and drug approaches. Results Epidemiological studies indicate that NAFLD raises risk of fatal or non‐fatal CVD events. NAFLD patients have a higher prevalence of arterial plaques and stiffness, coronary calcification, and endothelial dysfunction. Although genetic and environmental factors strongly contribute to NAFLD pathogenesis, a Mendelian randomization analysis indicated that the PNPLA3 genetic variant leading to NAFLD may not be causally associated with CVD risk. Among other genetic variants related to NAFLD, TM6SF2 appears to be protective, whereas MBOAT7 may favour venous thromboembolism. Conclusions NAFLD is correlated to a higher CVD risk which may be ameliorated by dietary interventions. This is not surprising, since new criteria defining MAFLD include other metabolic risk abnormalities fuelling development of serious adverse extrahepatic outcomes, for example CVD. The present lack of a targeted pharmacological approach makes the identification of patients with liver disease at higher CVD risk (eg diabetes, hypertension, obesity or high levels of C‐reactive protein) of major clinical interest.

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“…Cytokine production is one of the most important properties of immune cells, as it orchestrates a functional immune response involving both cells of adaptive and innate immunity (29). In this study, we describe a method for intracellular cytokine staining in murine and human HSPCs.…”

Section: Discussionmentioning

confidence: 99%

Optimized Intracellular Staining Reveals Heterogeneous Cytokine Production Ability of Murine and Human Hematopoietic Stem and Progenitor Cells

et al. 2021

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Under stress conditions, hematopoietic stem and progenitor cells (HSPCs) can translate danger signals into a plethora of cytokine signals. These cytokines, or more precisely their combination, instruct HSPCs to modify the magnitude and composition of hematopoietic output in response to the threat, but investigations into the heterogeneous cytokine expression and regulatory mechanisms are hampered by the technical difficulty of measuring cytokine levels in HSPCs at the single-cell level. Here, we optimized a flow cytometry-based method for the simultaneous assessment of multiple intracellular cytokines in HSPCs. By selecting an optimal combination of cytokine restimulation reagents, protein transport inhibitors, and culture supplements, an optimized restimulation protocol for intracellular staining was developed. Using this method, we successfully examined expression levels of granulocyte/macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in murine and human HSPC subsets under steady-state or different stress conditions. Different cytokine expression patterns were observed, suggesting distinct regulatory modes of cytokine production dependent on the HSPC subset, cytokine, disease, organ, and species. Collectively, this technical advance may help to obtain a better understanding of the nature of HSPC heterogeneity on the basis of differential cytokine production.

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Immunopathobiology and therapeutic targets related to cytokines in liver diseases

Cited by 84 publications

References 308 publications

A new syndrome of moyamoya disease, kidney dysplasia, aminotransferase elevation, and skin disease associated with de novo variants in RNF213

A new syndrome of moyamoya disease, kidney dysplasia, aminotransferase elevation, and skin disease associated with de novo variants in RNF213

Nonalcoholic fatty liver disease or metabolic dysfunction‐associated fatty liver disease diagnoses and cardiovascular diseases: From epidemiology to drug approaches

Optimized Intracellular Staining Reveals Heterogeneous Cytokine Production Ability of Murine and Human Hematopoietic Stem and Progenitor Cells

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