Differential peripheral memory T cell subsets sensitively indicate the severity of nonalcoholic fatty liver disease

Kado, Akira; Tsutsumi, Takeya; Yotsuyanagi, Hiroshi; Ikeuchi, Kazuhiko; Okushin, Kazuya; Moriya, Kyoji; Koike, Kazuhiko; Fujishiro, Mitsuhiro

doi:10.1111/hepr.14009

Cited by 3 publications

(1 citation statement)

References 72 publications

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“…Mice pre-exposed to immune stimuli possess an increased number of CD8 + effector memory T cells, leading to more severe skin inflammatory responses compared to unstimulated mice ( 31 ). The frequencies of CD8 + TCM positively correlate with the degree of steatosis, lobular inflammation, and ballooning in non-alcoholic fatty liver disease ( 32 ). CD8 + TCM cells in the brain can trigger inflammation by reactivating and expanding in response to signals from glial cells, which leads to an influx of other immune cells and increased local microglial activity, intensifying the immune response ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Unraveling the immunological landscape in acute pancreatitis progression to sepsis: insights from a Mendelian randomization study on immune cell traits

Liu,

Wang,

Zhao

et al. 2024

Front. Immunol.

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BackgroundAcute pancreatitis (AP) is a severe digestive system disorder with a significant risk of progressing to sepsis, a major cause of mortality. Unraveling the immunological pathways in AP is essential for developing effective treatments, particularly understanding the role of specific immune cell traits in this progression.MethodsEmploying a bidirectional two-sample Mendelian Randomization (MR) approach, this study first examined the causal relationship between AP and 731 immune cell traits to identify those significantly associated with AP. Subsequently, we explored the causal associations between 731 immune cell traits and sepsis. The analysis utilized extensive genome-wide association studies (GWAS) summary datasets, with a focus on identifying common immune cell traits with statistically significant causal associations between AP and sepsis.ResultsOur investigation identified 44 immune cell traits unidirectionally associated with AP and 36 traits unidirectionally associated with sepsis. Among these, CD127 on CD28+ CD45RA- CD8+ T cells emerged as a common mediator, accounting for 5.296% of the increased risk of sepsis in AP patients. This finding highlights the significant role of specific memory CD8+ T cells in the pathophysiology of AP and its progression to sepsis.ConclusionThis study elucidates the critical role of specific immune cell traits, particularly CD127hi memory CD8+ T cells, in the progression of AP to sepsis. Our findings provide a foundation for future research into targeted immune-modulatory therapies, potentially improving patient outcomes in AP-related sepsis and offering new insights into the complex immunological dynamics of this condition.

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Section: Discussionmentioning

confidence: 99%

Unraveling the immunological landscape in acute pancreatitis progression to sepsis: insights from a Mendelian randomization study on immune cell traits

Liu,

Wang,

Zhao

et al. 2024

Front. Immunol.

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Decreased antioxidant-related superoxide dismutase 1 expression in peripheral immune cells indicates early ethanol exposure

Kado,

Moriya,

Inoue

et al. 2024

Sci Rep

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Alcohol consumption increases oxidative stress and imbalances in the antioxidant system, even with ethanol (EtOH) exposure at a young age. This study assessed changes in the antioxidant system following young EtOH exposure in peripheral immunity and measured sensitive indicators of heavy alcohol consumption. We used peripheral blood mononuclear cells (PBMCs) from 197 male university students without smoking habits to examine changes in antioxidant-related gene expression in vitro and in PBMCs. In vitro, the antioxidant system was impaired by EtOH. Next, we examined the expression of 84 antioxidant-related genes in the PBMCs of 162 young adults, among which the superoxide dismutase (SOD) 1 expression was most negatively correlated with alcohol consumption degree. The plasma SOD1 level had the highest area under the curve value (0.806) for heavy alcohol consumption. Our data demonstrated that a decreased SOD1 level is a sensitive indicator of an impaired antioxidant system and heavy alcohol consumption with early EtOH exposure. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-76084-8.

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Causal associations of immunophenotypes with metabolic dysfunction-associated fatty liver disease and mediating pathways: a Mendelian randomization study

Xie,

Chen,

et al. 2024

Therapeutic Advances in Chronic Disease

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Background: Increasing evidence suggests that immunophenotypes play a crucial role in Metabolic dysfunction-associated fatty liver disease (MAFLD), but the specific immunophenotypes contributing to its pathogenesis remain unclear. Objectives: This study aimed to elucidate the causal associations between immunophenotypes and MAFLD and identify the underlying mediation pathways involved. Design: Mendelian randomization (MR) study. Methods: This study is a quasi-causal inference analysis using univariable and multivariable MR (UVMR and MVMR). Five MAFLD genome-wide association studies (GWASs) and the largest immunophenotype GWAS were analyzed to assess their causal associations. Two-step MR identified potential mediators and quantified their mediation proportions. Comprehensive MR methods, multiple sensitivity analyses, meta-analyses, and false discovery rate (FDR) further enhanced the robustness of our findings. Results: Pooled inverse-variance weighted (IVW) estimates in UVMR identified 47 immunophenotypes having a suggestive causal association with MAFLD. After adjusting for FDR, three lymphocyte phenotypes remained significant: CD20 on IgD−CD24− B cells (OR: 1.035, pfdr: 0.006), terminally differentiated CD8+ T cells %T cells (OR: 1.052, pfdr: 0.006), and CD4 on CD39+ secreting CD4+ regulatory T cells (OR: 1.036, pfdr: 0.046). Meta-analysis of IVW MVMR estimates with confounders adjustment confirmed that CD20 on IgD−CD24− B cells and terminally differentiated CD8+ T cells %T cells had significant direct causal associations on MAFLD ( pfdr < 0.05). Additionally, two-step MR analysis identified the waist-to-hip ratio as a mediator, accounting for 42.64% of the causal association between CD20 on IgD−CD24− B cells and MAFLD. Conclusion: The causal associations of three lymphocyte phenotypes with increased MAFLD risk were identified in this study. CD20 on IgD−CD24− B cells may both directly and indirectly elevate MAFLD risk, while terminally differentiated CD8+ T cells have a direct causal relationship with MAFLD. These findings suggest new possibilities for targeted therapies and underscore the potential for personalized immunotherapy in managing MAFLD.

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Differential peripheral memory T cell subsets sensitively indicate the severity of nonalcoholic fatty liver disease

Cited by 3 publications

References 72 publications

Unraveling the immunological landscape in acute pancreatitis progression to sepsis: insights from a Mendelian randomization study on immune cell traits

Unraveling the immunological landscape in acute pancreatitis progression to sepsis: insights from a Mendelian randomization study on immune cell traits

Decreased antioxidant-related superoxide dismutase 1 expression in peripheral immune cells indicates early ethanol exposure

Causal associations of immunophenotypes with metabolic dysfunction-associated fatty liver disease and mediating pathways: a Mendelian randomization study

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