Phospholipase a2 contribution to thymocyte maturation and apoptotic thymocyte cell clearence

磷脂酶 a2 对胸腺细胞成熟和凋亡胸腺细胞清除的贡献

• 批准号: 386598-2011
• 负责人: Boilard, Eric
• 金额: $ 2.55万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=528963
• 关键词: Phospholipase; a2; contribution; thymocyte; maturation

The thymus is the organ where the maturation of T-cells occurs. Although the different stages of immature T-lymphocyte maturation have been described, the mechanisms implicated remain obscure and create fascination in the field of basic immunology. It is estimated that 50 million immature T-cells are generated each day in the thymus and that only 2 million ultimately leave the thymus and reach the blood circulation. Intriguingly, while most immature T-cells undergo cell death, only 1-2% can be detected as dying cells in the steady state, suggesting the existence of soluble signals delivered by the dying T-cells to promote prompt clearance by scavenger cells (phagocytes). Interestingly, the generation of lipid mediators was revealed to be a mechanism for lymphocyte maturation, though the role of lipid releasing enzymes phospholipase A2 (PLA2) in this process remained undefined. We found that secreted PLA2 group X - a secreted PLA2 mainly expressed in the thymus - participates to apoptotic thymocyte clearance. To gain further insight into PLA2 mechanism of action in T-lymphocyte maturation and apoptosis we will pursue the following Aims:

胸腺是 T 细胞成熟的器官。尽管已描述了未成熟 T 淋巴细胞成熟的不同阶段，但所涉及的机制仍然模糊，并在基础免疫学领域引起了人们的兴趣。据估计，胸腺中每天产生 5000 万个未成熟 T 细胞，最终只有 200 万个离开胸腺并进入血液循环。 有趣的是，虽然大多数未成熟的 T 细胞会发生细胞死亡，但只有 1-2% 的细胞在稳定状态下可以被检测到正在死亡，这表明死亡 T 细胞传递的可溶性信号的存在可促进清道夫细胞（吞噬细胞）的迅速清除。有趣的是，脂质介质的产生被揭示是淋巴细胞成熟的一种机制，尽管脂质释放酶磷脂酶 A2 (PLA2) 在此过程中的作用仍不清楚。我们发现分泌型 PLA2 X 组（主要在胸腺中表达的分泌型 PLA2）参与凋亡胸腺细胞清除。为了进一步了解 PLA2 在 T 淋巴细胞成熟和凋亡中的作用机制，我们将追求以下目标：