CARD9 deficiency aggravated nonalcoholic steatohepatitis in mice through increasing inflammatory response

Liu, Xin; Fang, Yi; Qian, Chenchen; Chen, Jiahao; Luo, Wu; Zuo, Wei; Lin, Jianjun; Xie, Longteng; Liang, Guang; Huang, Lijiang; Wang, Yi

doi:10.1016/j.bbadis.2023.166893

Cited by 2 publications

(3 citation statements)

References 47 publications

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“…It was reported that an inhibitor of Syk, a downstream mediator of Dectin‐1, suppressed the pathogenesis of NASH (Kurniawan et al, 2018). On the other hand, deficiency of Card9, a major downstream molecule of Syk, exacerbated NASH (Liu et al, 2024). This may be due to the suppression of the anti‐inflammatory response in Card9‐deficient mice (Liu et al, 2024).…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, deficiency of Card9, a major downstream molecule of Syk, exacerbated NASH (Liu et al, 2024). This may be due to the suppression of the anti‐inflammatory response in Card9‐deficient mice (Liu et al, 2024). Indeed, several C‐type lectin receptors can produce IL‐10, an anti‐inflammatory cytokine, via Card9 (LeibundGut‐Landmann et al, 2007; Robinson et al, 2009) as well as inflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

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Self‐recognition through Dectin‐1 exacerbates liver inflammation

Torigoe,

Lowman,

Sugiki

et al. 2024

Genes to Cells

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Dectin‐1 is a well‐characterized C‐type lectin receptor involved in anti‐fungal immunity through the recognition of polysaccharides; however, molecular mechanisms and outcomes initiated through self‐recognition have not been fully understood. Here, we purified a water‐soluble fraction from mouse liver that acts as a Dectin‐1 agonist. To address the physiological relevance of this recognition, we utilized sterile liver inflammation models. The CCl4‐induced hepatitis model showed that Dectin‐1 deficiency led to reduced inflammation through decreased inflammatory cell infiltration and lower pro‐inflammatory cytokine levels. Moreover, in a NASH model induced by streptozotocin and a high‐fat diet, hepatic inflammation and fibrosis were ameliorated in Dectin‐1‐deficient mice. The Dectin‐1 agonist activity was increased in the water‐soluble fraction from NASH mice, suggesting a potential pathogenic cycle between Dectin‐1 activation and hepatitis progression. In vivo administration of the fraction into mice induced hepatic inflammation. These results highlight a role of self‐recognition through Dectin‐1 that triggers hepatic innate immune responses and contributes to the exacerbation of inflammation in pathogenic settings. Thus, the blockade of this axis may provide a therapeutic option for liver inflammatory diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Self‐recognition through Dectin‐1 exacerbates liver inflammation

Torigoe,

Lowman,

Sugiki

et al. 2024

Genes to Cells

View full text Add to dashboard Cite

show abstract

“…Qi et al found that CXCL5 increased the lipid toxicity of hepatocytes by up-regulating NLRP3/caspase1/IL-1b signaling in KCs and exerting its pro-inflammatory properties (49). Liu et al confirmed that CARD9 deficiency induces S100a8/a9 expression through tolllike receptors, leading to increased expression of pro-inflammatory, fibrotic, and lipid metabolism-related genes in NASH progression (50). In addition, in NAFLD, platelets are highly activated and participate in disease progression by enhancing the pro-thrombotic and pro-inflammatory states.…”

Section: Discussionmentioning

confidence: 99%

Systemic immune-inflammatory biomarkers (SII, NLR, PLR and LMR) linked to non-alcoholic fatty liver disease risk

Liu,

Tang,

Liu

et al. 2024

Front. Immunol.

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BackgroundSystemic immune-inflammatory biomarkers including systemic immune inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) have been demonstrated to be associated with the risk and severity of various liver diseases. However, studies on their role and clinical significance in metabolic diseases, especially in nonalcoholic fatty liver disease (NAFLD), are limited and results are inconsistent.Methods10821 adults aged 20 years or older were enrolled in this cross-sectional study, sourced from six cycles of the National Health and Nutrition Examination Survey (NHANES). Survey-weighted logistic regression was employed to investigate the correlation between systemic immune-inflammatory biomarkers (SII, NLR, PLR, and LMR) and NAFLD risk. Restricted cubic spline regression models and segmented regression models were used to describe nonlinear relationships and threshold effects. Subgroup and sensitivity analyses were also conducted.ResultsAfter adjusting for all confounding variables, there was a significant positive association observed between ln-transformed SII (OR= 1.46, 95% CI: 1.27-1.69, P <0.001), NLR (OR= 1.25, 95% CI: 1.05-1.49, P =0.015), LMR (OR= 1.39, 95% CI: 1.14-1.69, P = 0.002) with NAFLD. A nonlinear dose-response relationship with an inverted “U”-shaped threshold of 4.64 was observed between ln(PLR) and NAFLD risk. When ln(PLR) was below 4.64, each unit increase in ln(PLR) was associated with a 0.55-fold increase in the risk of NAFLD (OR= 1.55, 95% CI: 1.05-2.31, P <0.05). Conversely, when ln(PLR) exceeded 4.64, each unit increase in ln(PLR) was associated with a 0.40-fold decrease in the risk of NAFLD (OR= 0.60, 95% CI. 0.44-0.81, P <0.05).Conclusionln-transformed SII, NLR, and LMR were linearly associated with NAFLD risk. ln(PLR) showed an inverted “U”-shaped nonlinear dose-response relationship with the risk of NAFLD.

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CARD9 deficiency aggravated nonalcoholic steatohepatitis in mice through increasing inflammatory response

Cited by 2 publications

References 47 publications

Self‐recognition through Dectin‐1 exacerbates liver inflammation

Self‐recognition through Dectin‐1 exacerbates liver inflammation

Systemic immune-inflammatory biomarkers (SII, NLR, PLR and LMR) linked to non-alcoholic fatty liver disease risk

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