Up-regulation of miR-27a promotes monocyte-mediated inflammatory responses in Kawasaki disease by inhibiting function of B10 cells

Kawasaki disease (KD) is an acute systemic vasculitis and activation of monocytes plays a central role in the pathogenesis of it. B10 cells, a B cell subset with negative regulatory properties, are functionally identified by their ability to express cytoplasmic IL-10 after ex vivo stimulation. Here, we aimed to explore the functional role of B10 cells during monocyte-mediated inflammatory responses in KD, as well as elucidate the underlying microRNA (miRNA)-mediated regulatory mechanisms. Expression of IL-10 by each group of B cells (total B cells, transitional B cells, naive B cells, and memory B cells) and inhibition of monocyte-derived TNF-alpha by activated B cells were measured by flow cytometry. Expression of miRNAs (miR-21-3p, miR-98-5p/3p, miR-27a-3p, let7b-5p, and miR-1423p/5p) that affect IL-10 levels in B cells was quantitated by real-time PCR. The relationship between IL-10 and these miRNAs was examined by multivariate analysis. MiR-mediated RNA interference in B cells was performed to investigate the role of miR-27a on expression of IL-10. The results showed expression of cytoplasmic IL-10 in B cell subsets from patients with KD was down-regulated. The inhibitory effect of B10 cells on production of TNF-alpha by monocytes from patients with KD was also compromised. The miR-27a-3p expression was markedly up-regulated during the acute phrase of KD, and it promoted monocyte-mediated TNF-alpha release by negatively regulating expression of cytoplasmic IL-10 within B cells in vitro. The data suggest up-regulated miR-27a in B cells from patients with KD may promote monocyte-mediated inflammatory responses by inhibiting the regulatory function of B10 cells.