Abstract
Small non-coding microRNAs (miRNAs) have been found to play critical roles in many biological processes by controlling gene expression at the post-transcriptional level. They appear to fine-tune the immune response by targeting key regulatory molecules, and their abnormal expression is associated with immune-mediated inflammatory disorders. Monocytes actively contribute to tissue homeostasis by triggering acute inflammatory reactions as well as the resolution of inflammation and tissue regeneration, in case of injury or pathogen invasion. Their contribution to tissue homeostasis can have many aspects because they are able to differentiate into different cell types including macrophages, dendritic cells, and osteoclasts, which fulfill functions as different as bone remodeling and immune response. Monocytes consist of different subsets with subset-specific expression of miRNAs linked to distinct biological processes dedicated to specific roles. Therefore, understanding the role of miRNAs in the context of monocyte heterogeneity may provide clues as to which subset gives rise to which cell type in tissues. In addition, because monocytes are involved in the pathogenesis of chronic inflammation, associated with loss of tissue homeostasis and function, identifying subset-specific miRNAs might help in developing therapeutic strategies that target one subset while sparing the others. Here, we give an overview of the state-of-the-art research regarding miRNAs that are differentially expressed between monocyte subsets and how they influence monocyte functional heterogeneity in health and disease, with descriptions of specific miRNAs. We also revisit the existing miRNome data to propose a canonical signature for each subset.
Highlights
MicroRNAs are a class of short non-coding RNAs (18–22 nt), conserved from worms to mammals that play a regulatory role in gene expression at the posttranscriptional level [1]
At the intersection of mouse datasets, we identified 4 miRNAs; miR-148a and miR-130b were upregulated in Ly6Chigh versus Ly6Clow monocytes
We give an overview of the state-of-the-art research of miRNAs that are differentially expressed between monocyte subsets and how they affect monocyte functional heterogeneity, with descriptions of functional and in silico studies of specific miRNAs
Summary
MicroRNAs (miRNAs) are a class of short non-coding RNAs (18–22 nt), conserved from worms to mammals that play a regulatory role in gene expression at the posttranscriptional level [1]. Our group showed that classical monocytes display reduced miR-146a expression in both arthritic humans and mice as compared with healthy individuals; in vivo delivery of miR-146a mimics into Ly6Chigh monocytes using a specific delivery system that spares Ly6Clow monocytes [58] rescued RelB expression in Ly6Chigh monocytes, reduced their capacity to differentiate into OCs and reduced inflammatory-mediated bone erosion in an experimental model of arthritis This is the first work to provide an in vivo proof of concept for a therapeutic strategy design targeting a subset-specific miRNA. Monitoring the repartition of monocyte subsets is an international recommendation as a diagnostic tool for patients with monocytosis to distinguish between chronic myelomonocytic leukemia and reactive monocytosis [63]
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