Siglec-G在抗感染T细胞免疫记忆形成中的作用及机制研究

项目名称： Siglec-G在抗感染T细胞免疫记忆形成中的作用及机制研究

项目编号： No.81471569

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 徐胜

作者单位： 中国人民解放军第二军医大学

项目金额： 71万元

中文摘要： 效应性CTL和记忆性CTL在机体抵抗病毒和胞内菌的初次和再次感染中发挥关键的保护作用，其形成过程也受到多种因素的精密调控。唾液酸结合凝集素Siglecs家族在识别病原体或者淋巴细胞表面糖链后，通过其胞内段的酪氨酸相关序列激活下游信号转导途径，广泛参与免疫应答各个过程的调控。本实验室曾报道过SiglecG在RNA病毒感染中，通过降解RIG-I负向调控干扰素产生和固有免疫应答。此次我们发现SiglecG在获得性免疫的记忆性CTL细胞高丰度表达，并且根据预实验推测SiglecG可能通过调控DC的抗原交叉递呈抑制效应性CTL形成，而CTL自身表达的SiglecG又参与了记忆性CTL细胞的产生和功能。本研究将进一步验证以上假说，明确SiglecG在抗感染获得性CTL应答众多效应及分子机制，为理解糖基修饰及糖基结合蛋白在T细胞应答中的作用提供实验依据，为感染性疾病的临床治疗提供潜在靶点。

中文关键词： 感染；免疫记忆；T细胞；树突状细胞；交叉递呈

英文摘要： Effector CTLs and memory CTLs play important protective roles in the primary and secondary infection of pathogens, especially virus and intracellular bacteria. The activation of effector CTLs and formation of memory CTLs are thus under precise control. Siglecs, a family of sialic acid binding lectins, can induce downstream signals and regulate the biological process of various immune responses after recognition of their ligands. We previously identified that SiglecG inhibit innate IFN-beta production by degradation of RIG-I when infectied with RNA virus. Here we found that only SiglecG was specifically upregulated in central memory T cells. With preliminary test, we hypothesized that SiglecG could suppressive effector CTL activation through suppress the cross presentation of DCs, while autologous SiglecG on CTL cells promoted memory T cell formation and function. The precise effects and detailed mechanisms of SiglecG in anti-infectious CTL responses need further identification, which will help our understanding of the function of Siglecs in the regulation of adaptive immune responses, and provide potential target sites for clinical therapy of infectious diseases.

英文关键词： infection;immunological memory;T cells;dendritic cell;cross presentation