Declined miR‐181a‐5p expression is associated with impaired natural killer cell development and function with aging

Lu, Jiao; Li, Shan; Li, Xiaopeng; Zhao, Wenming; Duan, Xuefeng; Gu, Xiuling; Xu, Jianqiao; Yu, Bolan; Sigal, Luis J.; Dong, Chen; Xie, Lixin; Fang, Min

doi:10.1111/acel.13353

Cited by 12 publications

(11 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, there are a number of studies reporting decreased levels of miR‐181 family members in the context of aging. For example, levels of specific miR‐181 homologs were found to be lower in serum from older individuals (Hooten et al, 2013), human naïve CD4+ T cells (Li, Yu, et al, 2012), murine NK cells (Lu et al, 2021), aged muscle (Mercken et al, 2013), and aged, calorie‐restricted brain tissue (Khanna et al, 2011). It will be interesting in future studies to explore the therapeutic potential of targeting miR‐181 homologs as a means to regulate immune cell responses, muscle function, chronic inflammation, bone repair, or other cellular processes that are known to be suppressed with increased age.…”

Section: Discussionmentioning

confidence: 99%

The miR‐181 family: Wide‐ranging pathophysiological effects on cell fate and function

Bell-Hensley

Das

McAlinden

2023

Journal Cellular Physiology

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are epigenetic regulators that can target and inhibit translation of multiple mRNAs within a given cell type. As such, a number of different pathways and networks may be modulated as a result. In fact, miRNAs are known to regulate many cellular processes including differentiation, proliferation, inflammation, and metabolism. This review focuses on the miR‐181 family and provides information from the published literature on the role of miR‐181 homologs in regulating a range of activities in different cell types and tissues. Of note, we have not included details on miR‐181 expression and function in the context of cancer since this is a broad topic area requiring independent review. Instead, we have focused on describing the function and mechanism of miR‐181 family members on differentiation toward a number of cell lineages in various non‐neoplastic conditions (e.g., immune/hematopoietic cells, osteoblasts, osteoclasts, chondrocytes, adipocytes). We have also provided information on how modulation of miR‐181 homologs can have positive effects on disease states such as cardiac abnormalities, pulmonary arterial hypertension, thrombosis, osteoarthritis, and vascular inflammation. In this context, we have used some examples of FDA‐approved drugs that modulate miR‐181 expression. We conclude by discussing some common mechanisms by which miR‐181 homologs appear to regulate a number of different cellular processes and how targeting specific miR‐181 family members may lead to attractive therapeutic approaches to treat a number of human disease or repair conditions, including those associated with the aging process.

show abstract

Section: Discussionmentioning

confidence: 99%

The miR‐181 family: Wide‐ranging pathophysiological effects on cell fate and function

Bell-Hensley

Das

McAlinden

2023

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…For example, miR-181a-5p was downregulated in aged NK cells, which inhibited NK cell development by reducing the production of IFNγ and the cytotoxicity of NK cells (Lu, Li, et al, 2021). MiR-181a was also downregulated in sarcopenia, an age-related loss of skeletal muscle mass and function, and negatively regulated myotube size (Soriano-Arroquia et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that reduced miR‐181a‐5p expression is associated with a series of age‐related disorders, including immune dysfunction (Kim et al, 2019 ; Lu, Li, et al, 2021 ), sarcopenia (Soriano‐Arroquia et al, 2016 ), and hearing loss (Zhang et al, 2013 ). For example, miR‐181a‐5p was downregulated in aged NK cells, which inhibited NK cell development by reducing the production of IFN‐γ and the cytotoxicity of NK cells (Lu, Li, et al, 2021 ). MiR‐181a was also downregulated in sarcopenia, an age‐related loss of skeletal muscle mass and function, and negatively regulated myotube size (Soriano‐Arroquia et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

MiR‐181a‐5p promotes neural stem cell proliferation and enhances the learning and memory of aged mice

Sun

Qiao

et al. 2023

Aging Cell

View full text Add to dashboard Cite

Hippocampal neural stem cell (NSC) proliferation is known to decline with age, which is closely linked to learning and memory impairments. In the current study, we found that the expression level of miR‐181a‐5p was decreased in the hippocampal NSCs of aged mice and that exogenous overexpression of miR‐181a‐5p promoted NSC proliferation without affecting NSC differentiation into neurons and astrocytes. The mechanistic study revealed that phosphatase and tensin homolog (PTEN), a negative regulator of the AKT signaling pathway, was the target of miR‐181a‐5p and knockdown of PTEN could rescue the impairment of NSC proliferation caused by low miR‐181a‐5p levels. Moreover, overexpression of miR‐181a‐5p in the dentate gyrus enhanced the proliferation of NSCs and ameliorated learning and memory impairments in aged mice. Taken together, our findings indicated that miR‐181a‐5p played a functional role in NSC proliferation and aging‐related, hippocampus‐dependent learning and memory impairments.

show abstract

“…First, the healthy donors were not age-matched as their median age was significantly lower than those of COVID-19 patients (39 years in HCs versus 60 years and 64 years in ICU and WARD respectively, Supplementary Table 1 ). Studies described that older people have a decreased proportion of CD56 bright versus CD56 dim NK cells and a decreased capacity to produce cytokines, chemokines, and cytotoxic molecules ( 71 , 72 ). Therefore, in the present study, the numerical differences in NK cells between patients and HCs, but not their cytotoxic and cytokine-producing activities, may be attributed to age differences.…”

Section: Discussionmentioning

confidence: 99%

Severe COVID-19 patients display hyper-activated NK cells and NK cell-platelet aggregates

et al. 2022

View full text Add to dashboard Cite

COVID-19 is characterised by a broad spectrum of clinical and pathological features. Natural killer (NK) cells play an important role in innate immune responses to viral infections. Here, we analysed the phenotype and activity of NK cells in the blood of COVID-19 patients using flow cytometry, single-cell RNA-sequencing (scRNA-seq), and a cytotoxic killing assay. In the plasma of patients, we quantified the main cytokines and chemokines. Our cohort comprises COVID-19 patients hospitalised in a low-care ward unit (WARD), patients with severe COVID-19 disease symptoms hospitalised in intensive care units (ICU), and post-COVID-19 patients, who were discharged from hospital six weeks earlier. NK cells from hospitalised COVID-19 patients displayed an activated phenotype with substantial differences between WARD and ICU patients and the timing when samples were taken post-onset of symptoms. While NK cells from COVID-19 patients at an early stage of infection showed increased expression of the cytotoxic molecules perforin and granzyme A and B, NK cells from patients at later stages of COVID-19 presented enhanced levels of IFN-γ and TNF-α which were measured ex vivo in the absence of usual in vitro stimulation. These activated NK cells were phenotyped as CD49a+CD69a+CD107a+ cells, and their emergence in patients correlated to the number of neutrophils, and plasma IL-15, a key cytokine in NK cell activation. Despite lower amounts of cytotoxic molecules in NK cells of patients with severe symptoms, majority of COVID-19 patients displayed a normal cytotoxic killing of Raji tumour target cells. In vitro stimulation of patients blood cells by IL-12+IL-18 revealed a defective IFN-γ production in NK cells of ICU patients only, indicative of an exhausted phenotype. ScRNA-seq revealed, predominantly in patients with severe COVID-19 disease symptoms, the emergence of an NK cell subset with a platelet gene signature that we identified by flow and imaging cytometry as aggregates of NK cells with CD42a+CD62P+ activated platelets. Post-COVID-19 patients show slow recovery of NK cell frequencies and phenotype. Our study points to substantial changes in NK cell phenotype during COVID-19 disease and forms a basis to explore the contribution of platelet-NK cell aggregates to antiviral immunity against SARS-CoV-2 and disease pathology.

show abstract

Declined miR‐181a‐5p expression is associated with impaired natural killer cell development and function with aging

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 12 publications

References 48 publications

The miR‐181 family: Wide‐ranging pathophysiological effects on cell fate and function

The miR‐181 family: Wide‐ranging pathophysiological effects on cell fate and function

MiR‐181a‐5p promotes neural stem cell proliferation and enhances the learning and memory of aged mice

Severe COVID-19 patients display hyper-activated NK cells and NK cell-platelet aggregates

Contact Info

Product

Resources

About