Otorhinolaryngology Hospital, the First Affiliated Hospital of Sun Yat-sen University, Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China.
Allergy. 2012 Mar;67(3):362-70. doi: 10.1111/j.1398-9995.2011.02776.x. Epub 2012 Jan 9.
MicroRNAs (miRNAs) are known to regulate the inflammatory response in various cell types. However, the ability of miRNAs to modulate dendritic cells (DCs) function for allergen immunotherapy is unclear.
To assess the role of miR-23b in the regulation of ovalbumin (OVA)-induced DC differentiation and function and to investigate the related molecular mechanisms.
Bone marrow-derived dendritic cells (BMDCs) were generated from murine bone marrow progenitor cells and subsequently stimulated with OVA to examine the profile of miRNA expression. After transfection with miR-23b reagents, DCs were evaluated for endocytic ability, surface marker expression, cytokine secretion and CD4+ T-cell differentiation. The possible roles of the Notch and NF-κB signalling pathways were also evaluated. Human monocyte-derived dendritic cells (MDDCs) were similarly evaluated as well.
Significant upregulation of miR-23b was observed in BMDCs pulsed with OVA. Following miR-23b transfection, BMDCs showed decreased OVA uptake, increased IL-10 production, decreased IL-12 production and an enhanced capacity to promote FoxP3+ CD4+ T regulatory cells (Tregs) differentiation. In addition, inactivation of the Notch1 and NF-κB signalling pathways were observed. Conversely, inhibition of miR-23b in BMDCs resulted in the opposite effects. In human MDDCs, miRNA23b transfection similarly increased IL-10 and decreased IL-12 production, and that treated human MDDCs induced increased FoxP3+ CD4+ T cells.
Our findings provide evidence that miR-23b is capable of inducing tolerogenic DC activity and Treg responses in vitro through the inhibition of the Notch1 and NF-κB signalling pathways; thus, miR-23b might represent a therapeutic target for the management of allergic diseases.
已知 microRNAs（miRNAs）可调节各种细胞类型的炎症反应。然而，miRNAs 调节树突状细胞（DC）功能用于变应原免疫治疗的能力尚不清楚。
评估 miR-23b 在调节卵清蛋白（OVA）诱导的 DC 分化和功能中的作用，并研究相关的分子机制。
从鼠骨髓祖细胞生成骨髓来源的树突状细胞（BMDCs），然后用 OVA 刺激以检查 miRNA 表达谱。用 miR-23b 试剂转染后，评估 DC 的内吞能力、表面标志物表达、细胞因子分泌和 CD4+T 细胞分化。还评估了 Notch 和 NF-κB 信号通路的可能作用。同样评估了人单核细胞来源的树突状细胞（MDDCs）。
在用 OVA 脉冲的 BMDCs 中观察到 miR-23b 的显著上调。miR-23b 转染后，BMDCs 表现出 OVA 摄取减少、IL-10 产生增加、IL-12 产生减少以及促进 FoxP3+CD4+T 调节细胞（Tregs）分化的能力增强。此外，还观察到 Notch1 和 NF-κB 信号通路失活。相反，在 BMDCs 中抑制 miR-23b 则产生相反的效果。在人 MDDCs 中，miRNA23b 转染同样增加了 IL-10 并减少了 IL-12 的产生，并且处理过的人 MDDCs 诱导了更多的 FoxP3+CD4+T 细胞。
我们的研究结果提供了证据，表明 miR-23b 通过抑制 Notch1 和 NF-κB 信号通路，能够在体外诱导耐受的 DC 活性和 Treg 反应；因此，miR-23b 可能成为管理过敏疾病的治疗靶点。
