Age-dependent loss of induced regulatory T cell function exacerbates liver ischemia-reperfusion injury

Li, Rui; Zhang, Shaopeng; Ma, Wenxuan; Lü, Hao; Gao, Junfang; Gan, Xiaojie; Ju, Zheng; Gu, Jian; Lü, Ling

doi:10.1016/j.molimm.2018.10.004

Cited by 9 publications

(5 citation statements)

References 33 publications

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“…Multiple alterations at the cellular and molecular levels contributed to the increased liver injury post‐IR in the aged mice, among which the enhanced inflammatory response has been shown to be an important factor (Kan et al, 2018). Age‐dependent loss of induced regulatory T‐cell function has also been shown to exacerbate liver IR injury in a recent study (Liu et al, 2018). However, controversial results have been found regarding the proinflammatory response of macrophages from young and aged subjects.…”

Section: Discussionmentioning

confidence: 94%

Aging aggravated liver ischemia and reperfusion injury by promoting STING‐mediated NLRP3 activation in macrophages

Zhong

Rao

et al. 2020

Aging Cell

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Section: Discussionmentioning

confidence: 94%

Aging aggravated liver ischemia and reperfusion injury by promoting STING‐mediated NLRP3 activation in macrophages

Zhong

Rao

et al. 2020

Aging Cell

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“…In xenograft, mouse models have verified that age is connected with changes in immune system [11, 12]. When compared with younger ones, older mice further proved modificative cytokine kinetics [13] and reduced CD8 + T cell proliferation [14], and this is also associated with the decrement in T cell function [15] and CD28 expression [16, 17], which is a co-stimulatory signal for T cell activation [18]. But in clinical trials, Elias et al [19] reviewed efficacy and safety of ICI in patients with non-small cell lung cancer, melanoma, and renal cancer and found that there were no obvious age-associated difference in overall survival (OS) and side effects among those older and younger patients.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Immune Checkpoint Inhibitors between Older and Younger Patients with Advanced or Metastatic Lung Cancer: A Systematic Review and Meta-Analysis

Zhang

Sun

et al. 2019

BioMed Research International

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Objectives. Despite the fact that it is widely acknowledged that immune checkpoint inhibitors (ICIs) rely on the presence of immune response to take their antitumor effect, little is known whether there is an influence exerted on the efficacy of ICIs based on patients’ age. We performed a systematic review and meta-analysis to explore the efficacy of ICIs between younger and older patients. Materials and Methods. We searched online database and major conference proceedings for randomized controlled trials (RCTs) published of ICIs and included RCTs that conducted subgroup comparisons of age with available combination of hazard ratios (HRs) and 95% confidence interval (95%CI). Subsequently, we figured out the pooled HR and 95%CI in younger and older patients with a random-effects model and evaluated the within-study heterogeneity by using subgroup, sensitivity, and meta-regression analysis. Results and Conclusion. A total of 12 eligible RCTs included in our study, which reported OS according to patients’ age. The overall estimated random-effects for HR was 0.75 with 95% CI of 0.65-0.87 in younger arm versus 0.81 with 95% CI of 0.72-0.92 in older arm. ICIs can improve OS for patients with advanced or metastatic lung cancer when compared to controls, especially for those patients with NSCLC, anti-PD-1/PD-L1 inhibitors, non-squamous, Pembrolizumab or Atezolizumab used as well as subsequent-line setting, and the magnitude of benefit in OS had comparable efficacy in both younger and older arms using a cut-off of 65 yr. Conversely, we also drew a statically significant conclusion that older patients failed to acquire benefit from ICIs when subdivided with a further cut-off of 75 yr.

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“…Future studies including both in vitro and in vivo experiments are required to validate these early findings. Many studies have explored the association between older age and increased vulnerability to hepatic liver damage in I/R injury models [22,23].…”

Section: Discussionmentioning

confidence: 99%

“…Many studies have explored the association between older age and increased vulnerability to hepatic liver damage in I/R injury models 22 , 23 . Here we used three methods to explore the association of age and the severity of injury in a hepatic I/R model in older versus younger mice.…”

Section: Discussionmentioning

confidence: 99%

Decreased miR-329-3p upregulates Adamts4 and Dnajb1 in mouse hepatic I/R injury in an age-independent manner

Zhu,

Duan,

Yang

et al. 2023

Int. J. Med. Sci.

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Introduction: Hepatic ischemia/reperfusion (I/R) injury is common after liver surgery, particularly in patients of older age. However, an understanding of the mechanism of injury remains incomplete. In this study, we explored the molecular mechanisms underlying hepatic I/R injury and associations with age in a murine model. Methods: Gene expression profiling datasets (GSE72315 and GSE10654) and a microRNA (miRNA) expression profiling dataset (GSE72315) were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) and miRNAs (DEMiRs) were identified using online GEO2R or R before and after hepatic I/R injury in mice. Significant Gene Ontology (GO) terms were analyzed with the DAVID functional annotation tool. The DEMiR-miRNA target gene (miRTG) networks were constructed with miRTarBase, and the differentially expressed miRNAs and genes were analyzed with real-time quantitative polymerase chain reaction and immunofluorescence staining. Results: Through bioinformatic analysis, seven novel candidate miRNAs were identified that may regulate the expression of nine genes in hepatic I/R injury. Before and after hepatic I/R injury, mmu-miR-9-5p, mmu-miR-329-3p, and mmu-miR-290a-5p showed significant differential expression both in young (1 month old) and old (1 year old) mice. miR-329-3p had the most significant differential expression, and its predicted target genes Adamts4 and Dnajb1 were also significantly upregulated. Conclusions:The decrease in miR-329-3p expression upregulated Adamts4 and Dnajb1 expression in mouse hepatic I/R injury in an age-independent manner. This finding contributes to our understanding of hepatic I/R injury, and highlights novel molecular targets for future therapeutic development.

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Age-dependent loss of induced regulatory T cell function exacerbates liver ischemia-reperfusion injury

Cited by 9 publications

References 33 publications

Aging aggravated liver ischemia and reperfusion injury by promoting STING‐mediated NLRP3 activation in macrophages

Aging aggravated liver ischemia and reperfusion injury by promoting STING‐mediated NLRP3 activation in macrophages

Comparison of Immune Checkpoint Inhibitors between Older and Younger Patients with Advanced or Metastatic Lung Cancer: A Systematic Review and Meta-Analysis

Decreased miR-329-3p upregulates Adamts4 and Dnajb1 in mouse hepatic I/R injury in an age-independent manner

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