Immune and central nervous system-related miRNAs expression profiling in monocytes of multiple sclerosis patients

Antonella Amoruso,Federica Scaroni,Maria Blonda,Claudia Verderio,Valeria Di Francescantonio,Maira Gironi,Carlo Avolio,Roberta Grasso,Roberto Furlan

doi:10.1038/s41598-020-63282-3

Antonella Amoruso, Federica Scaroni + Show 7 more

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https://doi.org/10.1038/s41598-020-63282-3

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It is widely recognized that monocytes-macrophages adopt a wide variety of phenotypes, influencing the inflammatory activity and demyelination in Multiple Sclerosis (MS). However, how the phenotype of human monocytes evolves in the course of MS is largely unknown. The aim of our preliminary study was to analyse in monocytes of relapsing-remitting and progressive forms of MS patients the expression of a set of miRNAs which impact monocyte-macrophage immune function and their communication with brain cells. Quantitative PCR showed that miRNAs with anti-inflammatory functions, which promote pro-regenerative polarization, are increased in MS patients, while pro-inflammatory miR-155 is downregulated in the same patients. These changes may indicate the attempt of monocytes to counteract neuroinflammation. miR-124, an anti-inflammatory marker but also of myeloid cell quiescence was strongly downregulated, especially in progressive MS patients, suggesting complete loss of homeostatic monocyte function in the progressive disease phase. Profiling of miRNAs that control monocyte polarization may help to define not only the activation state of monocytes in the course of the disease but also novel pathogenic mechanisms.

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It is widely recognized that monocytes-macrophages adopt a wide variety of phenotypes, influencing the inflammatory activity and demyelination in Multiple Sclerosis (MS)
Significance levels and fold differences were calculated for the RRMS patients, PPMS patients and controls; the criterion for differential expression of miRNA was set to P < 0,05
Increased expression levels of miR-146a (Fig. 1a), miR-223 (Fig. 1b), miR-125a (Fig. 1c) miR-30c (Fig. 1d), and miR-23a (Fig. 1e) were found in both RRMS and PPMS patients as compared to controls. miR-181a (Fig. 1f) was augmented in RRMS but not in PPMS patients compared to healthy donors (HDs)

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It is widely recognized that monocytes-macrophages adopt a wide variety of phenotypes, influencing the inflammatory activity and demyelination in Multiple Sclerosis (MS). The aim of our preliminary study was to analyse in monocytes of relapsing-remitting and progressive forms of MS patients the expression of a set of miRNAs which impact monocyte-macrophage immune function and their communication with brain cells. Quantitative PCR showed that miRNAs with anti-inflammatory functions, which promote pro-regenerative polarization, are increased in MS patients, while pro-inflammatory miR155 is downregulated in the same patients. These changes may indicate the attempt of monocytes to counteract neuroinflammation. MiR-124, an anti-inflammatory marker and of myeloid cell quiescence was strongly downregulated, especially in progressive MS patients, suggesting complete loss of homeostatic monocyte function in the progressive disease phase. MiRNAs are released by brain cells and circulate in human body fluids bound to RNA-processing molecules or packaged inside extracellular vesicles (EVs), where they may reflect alterations of the brain status, representing a brain “fluid biopsy”[15,16,17]

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