Phospholipase a2 contribution to thymocyte maturation and apoptotic thymocyte cell clearence

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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: