MicroRNA target Fc receptors to regulate Ab-dependent Ag uptake in primary macrophages and dendritic cells
MicroRNA target Fc receptors to regulate Ab-dependent Ag uptake in primary macrophages and dendritic cells
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DOI：
10.1177/1753425916661042
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发表时间：
2016-10-01
期刊：
影响因子：
3.2
通讯作者：
Nares, Salvador
中科院分区：
文献类型：
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作者：
Naqvi, Afsar Raza;Fordham, Jezrom B.;Nares, Salvador
吞噬作用从颗粒内化开始，以先天和适应性免疫反应的激活为高潮。然而，mirna在吞噬作用中的作用在很大程度上仍然未知。在这项研究中，我们检测了miR-24、miR-30b和miR-142-3p在巨噬细胞（M phi）和树突状细胞（DC）介导的Ab Fc受体（FcR）吞噬中的作用。这些mirna的表达在被igg活化的微球和大肠杆菌吞噬后降低，表明它们在这一过程中起调节作用。此外，这些mirna的过表达损害了igg包被乳胶珠的摄取，这证实了促炎细胞因子TNF-和IL-8的分泌减少，PKC-的下调，以及超氧化物生成酶NADPH氧化酶2的表达水平。在机制上，转染miRNA模拟物的mphi和DC显示FcRs（包括FCGR2A、FcR1G和FCER2）的表达显著降低。我们发现FcR1G的表达不受转录水平的影响，而是受miR-30b的转录后调控。最后，我们证明了sirna介导的FcR1G敲低会导致igg磷酸化小珠的摄取减少，这表明它参与了抗体介导的吞噬作用。这些结果揭示了miR-24， miR-30b和miR-142-3p是fcr介导的吞噬和相关先天免疫反应的重要组成部分。
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 (M phi) 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- and IL-8 and down-regulation of PKC-, as well as superoxide-generating enzyme NADPH oxidase 2 expression level. Mechanistically, M phi and DC transfected with miRNA mimics show marked reduction in expression of FcRs including FCGR2A, FcR1G and FCER2. We show that FcR1G 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 FcR1G 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.