Regulation of IgG Sialylation

项目摘要： 血浆免疫球蛋白唾液酸度降低与多种炎症性疾病之间的关系 几十年来一直为人所知。已经深入研究了免疫球蛋白唾液酸化变化的下游影响，以及 现在认为唾液酸化的减少增加了免疫球蛋白G对激活Fc受体的亲和力，从而 推动整个身体的免疫激活。尽管调节失调的免疫球蛋白唾液酸化的下游效应 虽然已经有很好的文献记载，但控制免疫球蛋白唾液酸化的调节机制仍不清楚。如果这些 其作用机制已阐明，可作为调控免疫球蛋白功能的新靶点。 增强或抑制基于免疫球蛋白的炎症，视情况而定。之前的研究已经 这表明，与许多其他糖蛋白不同，免疫球蛋白在分泌过程中不能有效地进行唾液酸化， 指出了一种B细胞的外在机制，在这种机制中，免疫球蛋白唾液酸化在其释放后被动态调节 进入血液中。因此，拟议研究的目标是(1)确定关键的监管机制 潜在的免疫球蛋白唾液酸化和(2)阐明炎症信号如何转化为免疫球蛋白的变化 多聚糖。这项研究的成功将以揭示一种新颖而动态的调控机制为特征 通过调节多糖唾液酸化的变化来发挥免疫球蛋白的功能，同时提供尖端的科学和 融合了糖生物学和免疫学的专业培训，以促进专注于 在基于免疫球蛋白的治疗和转化科学方面处于领先地位。

Project Abstract: The association between decreased plasma IgG sialylation and a variety of inflammatory diseases has been known for decades. The downstream effects of changes in IgG sialylation have been studied in depth, and it is now believed that decreases in sialylation increase the affinity of IgG for activating Fc receptors, thereby driving immune activation throughout the body. Although the downstream effects of dysregulated IgG sialylation have been well documented, the regulatory mechanisms controlling IgG sialylation remain unknown. If these mechanisms are elucidated, they may serve as novel therapeutic targets to manipulate IgG function to either enhance or suppress IgG-based inflammation, depending on the circumstances. Previous research has suggested that, unlike many other glycoproteins, IgG is not sialylated efficiently during the secretory process, pointing to a B cell-extrinsic mechanism in which IgG sialylation is dynamically regulated following its release into the bloodstream. Therefore, the goals of the proposed studies are (1) to identify key regulatory mechanisms underlying IgG sialylation and (2) to elucidate how inflammatory signals are translated into changes in the IgG glycan. The success of this study will be characterized by revealing a novel and dynamic mechanism regulating IgG function through regulated changes in glycan sialylation, while providing cutting-edge scientific and professional training that blends both glycobiology and immunology to facilitate a career trajectory focused upon leadership in IgG-based therapies and translational science.