Siglec-F and Resolution of Allergic Inflammation

摘要 虽然对过敏性疾病中炎症反应的诱导有很多了解， 炎症，远没有了解的内源性机制，自然下降- 调节过敏性炎症反应。这些内源性反应可能 可能被利用来开发新的抗炎疗法， 过敏性疾病在本提案中，我们建议调查 Siglec-F（唾液酸结合Ig-超家族凝集素-F）细胞表面受体的活化 在下调过敏性鼻炎的炎症和组织重塑反应中发挥作用， 炎症Siglec-F在与过敏性炎症相关的细胞上高度表达 如嗜酸性粒细胞。Siglec-F受体在调节变态反应中的功能作用 反应是从它们的ITIM基序的细胞质尾部的存在， 参与免疫系统中的抑制信号通路。因此我们 建议确定1）Siglec-F发挥这种抗过敏作用的机制 体内和体外，和2）鉴定和表征Siglec-F特异性配体，其可 在体内变应性炎症反应期间由上皮细胞产生，（如它们的 名称意味着Siglecs与表达聚糖唾液酸的配体结合），以及3） 表征Siglec-8（小鼠Siglec-F的人直系同源物）的表达， 哮喘患者嗜酸性粒细胞炎症部位的配体。

Abstract While much is known about the induction of the inflammatory response in allergic inflammation, far less is understood about endogenous mechanisms that naturally down- regulate allergic inflammatory responses. These endogenous responses could potentially be harnessed to develop novel anti-inflammatory therapies for hypersensitivity diseases. In this proposal we propose to investigate the role that activation of Siglec-F (Sialic acid-binding Ig-superfamily lectin-F) cell surface receptors play in down-regulating the inflammatory, and tissue remodeling response in allergic inflammation. Siglec-F is highly expressed on cells associated with allergic inflammation such as eosinophils. A functional role for Siglec-F receptors in regulating allergic responses is suggested from the presence in their cytoplasmic tails of ITIM motifs know to be involved in inhibitory signaling pathways in the immune system. We therefore propose to determine 1) the mechanisms by which Siglec-F exerts this anti-allergic effect in vivo and in vitro, and 2) identify and characterize ligands specific for Siglec-F that may be generated by epithelium during an allergic inflammatory response in vivo, (as their name implies Siglecs bind to ligands expressing the glycan sialic acid), and 3) characterize the expression of Siglec-8 (the human orthologue of mouse Siglec-F) and its ligand at sites of eosinophilic inflammation in humans with asthma.