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

Abstract

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.

Figure 1

miRNAs expression levels in monocytes of HDs and MS patients by Real-Time PCR. Quantitative Real-Time PCR analysis of (a) mir-146a; (b) mir-223; (c) mir-125a; (d) mir-30c; (e) mir-181a; (f) mir-23a; (g) mir-155; (h) miR-124 was performed. The relative expression levels were calculated using the comparative Ct method, with RNU1A1 as endogenous control. Data are expressed as mean ± SEM of fold change values (*p < 0.05; **p < 0.01; ***p < 0.001), Kruskal-Wallis followed by Mann Whitney U test.

Figure 2

Phenotypic mRNAs expression levels in monocytes of HDs and MS patients by Real-Time PCR. Quantitative Real-Time PCR analysis of (a) IL-1β; (b) TNF-α; (c) IL-10; (d) CHI3L1 was performed. The relative expression levels were calculated using the comparative Ct method, with ACT-β as endogenous control. Data are expressed as mean ± SEM of fold change values (*p < 0.05; **p < 0.01; ***p < 0.001), Kruskal-Wallis followed by Mann Whitney U test.