MicroRNA target Fc receptors to regulate Ab-dependent Ag uptake in primary macrophages and dendritic cells

Abstract

Phagocytosis commences with particle internalization and culminates with the activation of innate and adaptive immune responses. However, the role of miRNAs in phagocytosis remains largely unknown. In this study, we examined the role of miR-24, miR-30b and miR-142-3p in Ab Fc receptor (FcR)-mediated phagocytosis by macrophages (MΦ) and dendritic cells (DC). The expression of these miRNAs was reduced following phagocytosis of both IgG-opsonized beads and Escherichia coli, indicating their regulatory role in the process. Further, overexpression of these miRNAs impaired the uptake of IgG-coated latex beads, which corroborated the reduced secretion of the pro-inflammatory cytokines TNF-α and IL-8 and down-regulation of PKC-α, as well as superoxide-generating enzyme NADPH oxidase 2 expression level. Mechanistically, MΦ and DC transfected with miRNA mimics show marked reduction in expression of FcRs including FCGR2A, FcɛR1G and FCER2. We show that FcɛR1G expression is not affected at the transcription level, rather it is post-transcriptionally regulated by miR-30b. Finally, we demonstrate that siRNA-mediated knockdown of FcɛR1G leads to reduced uptake of IgG-opsonized beads, indicating its involvement on Ab-mediated phagocytosis. These results uncover miR-24, miR-30b and miR-142-3p as an essential component of FcR-mediated phagocytosis and associated innate immune responses.