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Real-time quantitative PCR analysis of EV-associated miRNAs from Human Treg cells

ABSTRACT: MicroRNAs (miRNAs) are small non-coding molecules targeting messenger RNAs and inhibiting protein translation. Regulated by dynamic micro-environmental cues, miRNAs in turn modulate key biological processes, including cell growth and development, energy utilization and homeostasis. In particular, miRNAs control the differentiation, survival and activation of both CD4+ T conventional (Tconv) and CD4+ T regulatory (Treg) cells, key players of the adaptive immunity; in particular, miRNA-mediated gene expression regulation contributes to the physiological response of those cells to infections and the pathological loss of immune homeostasis in autoimmunity. Upon T cell receptor (TCR) stimulation, Treg cells release a fingerprint of miRNAs in association with extracellular vesicles (EVs), which is specific and significantly different from that released by Tconv cell counterpart (GSE183713). In this study, we have highlithed how Treg-cell derived EVs, and their miRNA content, are able to block the proliferation and activation of Tconv cells, demonstrating a strong tolerogenic function.

ORGANISM(S): Homo sapiens

PROVIDER: GSE209714 | GEO | 2025/03/20

REPOSITORIES: GEO

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Real-time quantitative PCR analysis of EV-associated miRNAs from Human Tconv cell

Project description:MicroRNAs (miRNAs) are small non-coding molecules targeting messenger RNAs and inhibiting protein translation. Regulated by dynamic micro-environmental cues, miRNAs in turn modulate key biological processes, including cell growth and development, energy utilization and homeostasis. In particular, miRNAs control the differentiation, survival and activation of CD4+ T conventional (Tconv) cells, key players of the adaptive immunity and miRNA-mediated gene expression regulation contributes to the physiological response to infections and the pathological loss of immune homeostasis in autoimmunity. Upon T cell receptor (TCR) stimulation, the described global miRNA quantitative decrease occurring in T cells is believed to promote the acquisition of effector functions by relaxing the post-transcriptional repression of genes associated to proliferation and cell activity. While miRNAs were initially thought to get down-regulated uniquely by intracellular degradation, miRNA secretion via extracellular vesicles (EVs) represents an additional mechanism of rapid down-regulation. By focusing on molecular interactions by means of graph theory, we have found that miRNAs released by TCR stimulated Tconv cells are significantly enriched for targeting transcripts up-regulated upon stimulation, including those encoding for crucial proteins associated to Tconv cell activation and function. Based on this computational approach, we present our perspective based on the following hypothesis: a stimulated Tconv cell will release miRNAs targeting genes associated to the effector function in the extracellular space in association with EVs, which will thus possess a suppressive potential toward other Tconv cells in the paracrine environment. We also propose possible future directions of investigation aimed at taking advantage of these phenomena to control Tconv cell effector function in health and autoimmunity.

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