Phospholipase a2 contribution to thymocyte maturation and apoptotic thymocyte cell clearence

胸腺是t细胞成熟发生的器官。尽管未成熟t淋巴细胞成熟的不同阶段已经被描述，但其机制仍然不清楚，并在基础免疫学领域产生了吸引力。据估计，胸腺每天产生5000万个未成熟的t细胞，其中只有200万个最终离开胸腺进入血液循环。有趣的是，虽然大多数未成熟的t细胞会发生细胞死亡，但在稳定状态下，只有1-2%的t细胞可以被检测到死亡细胞，这表明死亡t细胞传递的可溶性信号可以促进清道夫细胞（吞噬细胞）的迅速清除。有趣的是，脂质介质的产生被揭示为淋巴细胞成熟的一种机制，尽管脂质释放酶磷脂酶A2 （PLA2）在这一过程中的作用尚不明确。我们发现分泌PLA2组X -一个主要表达于胸腺的分泌PLA2 -参与胸腺细胞凋亡的清除。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，我们将进行以下研究：

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: