Mechanisms of Action of Extracorporeal Photopheresis in the Control of Bronchiolitis Obliterans Syndrome (BOS): Involvement of Circulating miRNAs

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Abstract

Clinical evidence suggests an improvement or stabilization of lung function in a fraction of patients with bronchiolitis obliterans syndrome (BOS) treated by extracorporeal photopheresis (ECP); however, few studies have explored the epigenetic and molecular regulation of this therapy. The aim of present study was to evaluate whether a specific set of miRNAs were significantly regulated by ECP. Total RNA was isolated from serum of patients with established BOS grade 1–2 prior to the start and after 6 months of ECP treatment. We observed a significant downregulation of circulating hsa-miR-155-5p, hsa-miR-146a-5p and hsa-miR-31-5p in BOS patients at the start of ECP when compared to healthy subjects. In responders, increased miR-155-5p and decreased miR-23b-3p expression levels at 6 months were found. SMAD4 mRNA was found to be a common target of these two miRNAs in prediction pathways analysis, and a significant downregulation was found at 6 months in PBMCs of a subgroup of ECP-treated patients. According to previous evidence, the upregulation of miR-155 might be correlated with a pro-tolerogenic modulation of the immune system. Our analysis also suggests that SMAD4 might be a possible target for miR-155-5p. Further longitudinal studies are needed to address the possible role of miR-155 and its downstream targets.

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Bozzini, S., Del Fante, C., Morosini, M., Berezhinskiy, H. O., Auner, S., Cattaneo, E., … Meloni, F. (2022). Mechanisms of Action of Extracorporeal Photopheresis in the Control of Bronchiolitis Obliterans Syndrome (BOS): Involvement of Circulating miRNAs. Cells, 11(7). https://doi.org/10.3390/cells11071117

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