FcRn在奶山羊乳腺IgG转运中的作用及其调控机理研究

The immunoglobulin G (IgG) from milk of dairy cattle and goat provides passive immunity and protection for newborn ruminants and humans. Increase the concentration of IgG in the milk plays important role in the development of modern dairy industry in China. Neonatal Fc receptor (FcRn) plays key role in transportation of IgG from blood stream to milk. Therefore, in this study, we investigate the effects and regulatory mechanism of FcRn on IgG transport in mammary gland of dairy goats. Firstly, the function of FcRn was identified based on the expression/location of FcRn in the mammary gland and its relationship with IgG content in milk and serum, and the direction and efficiency of IgG transportation was also investigated. Secondly, the regulatory patterns and the major factors affecting FcRn expression and IgG transportation were investigated using lactogenic hormones, acid-based treatment, and substrates treatment. Thirdly, the possible mechanism of glucocorticoids receptor (GR) regulating FcRn expression directly or by affecting NF-κB signaling pathway was investigated. The results of this study will provide scientific basis for regulating the IgG concentration in milk, and facilitate the development of dairy industry in China.

牛羊乳来源的IgG不仅能为初生反刍动物提供被动免疫，还可为人类提供免疫保护。提高乳中IgG含量，研究开发富含IgG的功能乳品是我国现代奶业发展的新方向。FcRn作为IgG的转运工具，是决定奶中IgG含量的关键因素。但目前FcRn在反刍动物乳腺IgG转运中的作用、特征及其调控机理尚不清楚。因此，本项目围绕奶山羊乳腺FcRn开展以下研究：1）从FcRn在乳腺表达定位及其与血/乳中IgG含量相关性入手，结合IgG转运方向和转运效率研究，阐明FcRn在山羊乳腺IgG转运中的作用；2）从激素应答性、酸碱度偏好特性和饱和动力学特性等方面，解析调控FcRn表达和IgG转运的主要因素；3）以GR调控通路为深入点，探明GR直接或通过NF-κB信号通路参与FCGRT基因表达和IgG转运过程中的分子机理。本项目的实施和研究成果，不仅为提高乳中IgG含量提供科学依据，还为我国奶业的升级转型奠定实践基础。

免疫球蛋白转运载体FcRn作为IgG的转运工具，是决定奶中IgG含量的关键因素。本研究以免疫球蛋白转运载体FcRn为研究对象，从不同泌乳阶段奶山羊乳腺组织到体外培养奶山羊乳腺上皮细胞，利用现代分子生物学和多组学技术，系统开展了FcRn在奶山羊乳腺IgG转运中的作用及其调控机理研究。结果表明：FcRn表达量与IgG转运之间存在正向相关关系，证明FcRn 在山羊乳腺IgG转运中发挥着重要作用；发现泌乳激素主要参与下调FCGRT表达和IgG 转运，而高浓度IgG和LPS可促进FcRn的表达和IgG转运；NF-κB信号通路和免疫相关通路在参与FcRn调控中可能起重要作用，关键基因可能是CXCL8和ENSCHIG00000026175基因；此外，发现NF-1转录因子可能是奶山羊乳腺FcRn介导的IgG转运调控中的关键靶点，其可能通过抑制FCGRT和B2M基因的表达发挥作用，在此过程中21_28135和chi-miR-221-3p可能参与其表达调控。上述研究结果为提高乳中IgG含量提供科学依据，也为以乳腺为生物反应器的免疫球蛋白生产奠定实践基础。