树突状细胞亚群吞噬凋亡细胞并诱导免疫耐受的分子机制研究

项目名称： 树突状细胞亚群吞噬凋亡细胞并诱导免疫耐受的分子机制研究

项目编号： No.81202306

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学免疫学、法医学

项目作者： 邱春红

作者单位： 山东大学

项目金额： 23万元

中文摘要： 机体内的凋亡细胞如果不能及时被清除则会导致自身免疫性疾病。经静脉注射进入小鼠体内的凋亡细胞，会随着静脉血进入脾脏的边缘区，并被脾脏的CD8a+CD103+DC亚群特异性地吞噬。而且该类细胞亚群的暂时缺失能够破坏机体针对凋亡细胞的自身免疫耐受，但是其识别凋亡细胞并参与免疫耐受的机制仍不清楚。已有的研究结果证明吞噬细胞能够通过自身表达的Tim4或MFG-E8等吞噬受体识别凋亡细胞，但是CD8a+CD103+DC亚群却不表达这些已知受体。因此，我们推测CD8a+CD103+DC亚群通过其自身的特定分子识别凋亡细胞。本项目旨在利用DC亚群免疫动物的方法获得针对这一细胞表面分子的系列抗体，并利用抗体阻断细胞表面分子的原理，筛选能够调控DCs识别凋亡细胞的特异性受体，从而明确DC识别凋亡细胞并诱导免疫耐受的相关机制。本项目的研究成果可以为凋亡细胞的清除障碍导致自身免疫性疾病的病因，病理及治疗提供线索。

中文关键词： DC；吞噬；凋亡细胞；；

英文摘要： In multicellular organisms, unnecessary or harmful cells are eliminated by apoptotic cell death. This elimination process is required to preserve tissue integrity and protect organisms from viral infection. After undergoing apoptosis, cell corpses are rapidly recognized and phagocytosed by phagocytic cells, such as macrophages and dendritic cells (DCs). Apoptotic cell clearance plays a critical role in the maintenance of self-tolerance, and that the impaired clearance of apoptotic cells is, at least, partly responsible for the etiology of autoimmune diseases. Intravenous injection of apoptotic cells could be dominantly engulfed by splenic CD8a + CD103 + DC located in the marginal zone of spleen. And the transient deletion of this DC subset caused the abberant immune tolerance induced by apoptotic cells clearance. However, the mechanism of the recognition of apoptotic cells by CD8a + CD103 + DC is still unclear. The previous research results showed that the phagocytic cells recognize apoptotic cells through their own phagocytic receptors, but CD8a + CD103 + DC subsets do not express the known phagocytic receptors: Tim4 and MFG-E8. Therefore, we speculate that the CD8a + CD103 + DC subsets express specific moleculars through which they can recognize apoptotic cells rapidly. To clarify the molecular mechanism

英文关键词： Dendritic cells；phagocytosis；apoptotic cell；；