Abstract
Brain ischemia induces systemic immunosuppression and increases a host's susceptibility to infection. MicroRNAs (miRNAs) are molecular switches in immune cells, but the alterations of miRNAs in human immune cells in response to brain ischemia and their impact on immune defense remain elusive. Natural killer (NK) cells are critical for early host defenses against pathogens. In this study, we identified reduced counts, cytokine production, and cytotoxicity in human peripheral blood NK cells obtained from patients with acute ischemic stroke. The extent of NK cell loss of number and activity was associated with infarct volume. MicroRNA sequencing analysis revealed that brain ischemia significantly altered miRNA expression profiles in circulating NK cells, in which miRNA-451a and miRNA-122-5p were dramatically upregulated. Importantly, inhibition of miR-451a or miR-122-5p augmented the expression of activation-associated receptors in NK cells. These results provide the first evidence that brain ischemia alters miRNA signatures in human NK cells.
Highlights
Infectious complications such as pneumonia and urinary tract infection account for about 20% of deaths in stroke victims
We found that the number of circulating Natural killer (NK) cells was significantly reduced after acute ischemic stroke (
This study provides the first evidence that acute ischemic stroke alters the expression pattern of miRNA in human NK cells
Summary
Infectious complications such as pneumonia and urinary tract infection account for about 20% of deaths in stroke victims. Evidence indicates that stroke induces severe suppression of systemic immunity, rendering patients susceptible for post-stroke infections [1,2,3]. A hallmark of stroke-induced immunodepression is lymphopenia, which is defined as a significant reduction of peripheral blood lymphocyte count [4,5,6]. The molecular mechanisms through which stroke suppresses systemic immune response in peripheral blood remain poorly understood. As non-coding RNAs with a length of 18-25 nucleotides, microRNAs (miRNAs) are recognized as major molecular switches that act as post-transcriptional repressors of protein-coding target messenger RNAs (mRNAs). By binding to the 3′-untranslated region (3′UTR), miRNAs induce the decay of mRNA molecules of target genes and inhibit their expression [8].
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