Role of polysialic acid in sex-specific immune responses

聚唾液酸(PolySia)是一种有效的免疫调节糖链，由长而线性的唾液酸残基链组成，这些唾液酸残基附着在健康成人细胞表面的一组有限的糖蛋白上。PolySia可促进细胞迁移并减弱免疫反应。然而，PolySia功能的分子细节尚未阐明，这在很大程度上是由于缺乏研究PolySia生物学所需的分析工具。我们最近开发了两种分析工具，可以用来研究PolySia。其中一个工具是一种新的用于定量血清中PolySia的ELISA，我们发现男性的PolySia浓度高于女性。我们感兴趣的是性别差异对一种有效的免疫调节多糖浓度的影响，了解这些差异的原因和结果构成了我的研究计划的基础。这项建议的目标是开发工具，通过1)确定血清PolySIA的性别差异的来源，2)开发鉴定多唾液酸化蛋白的方法，以及3)开发识别PolySia受体的方法。这项拨款中描述的方法将改变我们研究PolySia功能的分子基础的能力。

Polysialic acid (polySia) is a potent immunomodulatory glycan comprised of long, linear chains of sialic acid residues which are attached to a limited set of cell surface glycoproteins in healthy human adults. PolySia enables cell migration and attenuates the immune response. However, the molecular details of polySia function have not yet been elucidated, in large part due to the lack of analytical tools required to study polySia biology. We have recently developed two analytical tools which can be used to study polySia. One of these tools was a novel ELISA for quantifying polySia in serum and using it, we discovered that males have higher concentrations of polySia than females. We are interested in the implications of sex differences in concentration of a potent immunomodulatory glycan and understanding the causes and outcomes of these differences forms the basis of my research program. The goal of this proposal is to develop tools to enable this research program by 1) identifying the source of sex differences in serum polySia, 2) developing methodology to identify polysialylated proteins, and 3) developing methodology to identify polySia receptors. The methodology described in this grant will transform our ability to study the molecular basis for polySia function.