RNA结合蛋白quaking:单核-巨噬细胞分化及功能的重要调控者

The emerging roles of the RNA binding protein quaking in regulating differentiation and function of monocytes-macrophages

巨噬细胞是可塑性较强的一类固有免疫细胞,能够极化为不同表型,发挥吞噬、趋化等多种功能,参与疾病的发生发展。RNA结合蛋白quaking(QKI)通过影响RNA剪切、转位及表达等过程调控单核细胞分化、巨噬细胞极化及多种细胞功能。QKI调控单核细胞向巨噬细胞的分化,QKI缺失促进巨噬细胞极化为M1型,发挥促炎表型。相反,QKI过表达则促进其极化为M2型。除此以外,QKI还影响巨噬细胞吞噬受体、趋化因子表达。由于组织定居巨噬细胞特性存在差异,QKI调控巨噬细胞参与多种疾病发展(如动脉粥样硬化、炎症性肠病等)的调控机制多样。主要涉及cAMP反应元件结合蛋白(CREB)转录因子调控、信号转导子与转录激活子1/核因子κB(STAT1/NF-κB)炎症信号通路及吞噬受体mRNA前体剪接等。

Macrophages are a class of innate immune cells with strong plasticity.They can polarize into different phenotypes,serving with various functions,such as phagocytosis and chemotaxis,which is involved in the development of diseases.RNA-binding protein quaking(QKI)regulates monocyte differentiation,macrophage polarization and various cellular functions through RNA splicing,translocation and expression.QKI regulates the differentiation of monocytes into macrophages,and QKI deficiency promotes the polarization of macrophages into M1 type,which exerts a pro-inflammatory phenotype.In contrast,QKI overexpression promotes macrophage polarization into M2 type.Additionally,QKI affects macrophage phagocytic receptor and chemokine expression.Due to the variations in tissue-resident macrophages’features,QKI modulates macrophages in the pathogenesis of diseases(atherosclerosis,inflammatory bowel disease,etc.)through diverse mechanisms,which mainly involves cyclicAMP response element binding protein(CREB)transcription factor regulation,signal transducer and activator of transcription 1/nuclear factorκB(STAT1/NF-κB)inflammatory signaling pathway and pre-mRNA splicing of phagocytic receptor.