Ceramide-1-Phosphate: a new player in modulating DC in allergic airway inflammation!?

神经酰胺-1-磷酸盐：调节过敏性气道炎症 DC 的新参与者！？

• 批准号: 243108937
• 负责人: Professor Dr. Marco Idzko
• 金额: --
• 依托单位: Klinik für Innere Medizin II
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/243108937?language=en
• 关键词: Ceramide; Phosphate; new; player; modulating

Dendritic cells have been shown to be essential in the induction and maintenance of T helper 2 (TH2)-cell responses to inhaled allergens in asthma. Recent studies suggest that sphingolipid mediators (like ceramide, ceramide-1-phosphate (C1P) and sphingosine-1-phosphate (S1P)) are involved in regulating inflammation, via intracellular signalling pathway and/or binding to specific plasma-membrane receptors. While the role of S1P in the pathogenesis of asthma and DC biology has been extensively studied, little is know about C1P. Preliminary data by our group revealed that C1P might exert anti-inflammatory effects in acute allergic airway inflammation via modulation DC function. In the present study we want to investigate whether: 1) C1P can inhibit all cardinal features of acute and chronic experimental asthma; 2) C1P modulates the maturation, cytokine production and T cell priming capacity of bone marrow derived DC in vitro and in vivo 3) C1P effects the migration and TH2-priming of endogenous DC in vivo; 4) C1P influences maturation, cytokine production and T cell priming of human monocyte derived DC-function. 5) Does C1P interact with ORMDL-expression? 6) Finally, is C1P able to inhibit allergic airway inflammation in general and DC-driven humanized SCID-mouse model of asthma. This project will elucidate the role of C1P on DC-function in asthma.

树突状细胞已被证明是必不可少的诱导和维持辅助性T细胞2（TH 2）细胞的反应吸入过敏原在哮喘。最近的研究表明，鞘脂介质（如神经酰胺，神经酰胺-1-磷酸（C1 P）和鞘氨醇-1-磷酸（S1 P））参与调节炎症，通过细胞内信号通路和/或结合到特定的质膜受体。虽然S1 P在哮喘发病机制和DC生物学中的作用已被广泛研究，但对C1 P知之甚少。本课题组的初步研究结果表明，C1 P可能通过调节DC功能发挥其抗炎作用。本研究旨在探讨C1 P是否能抑制急、慢性实验性哮喘的所有主要特征; 2）C1 P在体内外对骨髓来源DC的成熟、细胞因子产生和T细胞启动能力的调节; 3）C1 P在体内对内源性DC的迁移和TH 2启动的影响; 4）C1 P影响人单核细胞衍生DC功能的成熟、细胞因子产生和T细胞引发。5)C1 P是否与ORMDL表达相互作用？6)最后，C1 P是否能够抑制一般过敏性气道炎症和DC驱动的人源化SCID小鼠哮喘模型。本项目将阐明C1 P在哮喘中对DC功能的作用。