成熟胸腺细胞的迁出对于外周T细胞免疫系统建立、T细胞受体库的多样性维持以及淋巴系统损伤后的重建具有重要意义。血管是胸腺细胞迁出的必经之路，但是，血管内皮细胞在胸腺细胞迁出过程中的调控机制，目前几乎完全不清楚。申请人团队最近发现血管内皮细胞上条件性缺失淋巴毒素beta受体（LTbR）导致成熟胸腺细胞迁出的严重缺陷，也提示成熟胸腺细胞利用其细胞表面的配体LT/LIGHT，通过LTbR受体作用于内皮细胞，自我反馈调节其迁出。在本项目中，申请人团队将利用相关的条件基因敲除小鼠，围绕LT/LIGHT-LTbR信号轴，阐明胸腺细胞与内皮细胞通过相互对话，调控胸腺细胞迁出的细胞和分子机制。此外，基于本团队最近关于胸腺血管内皮细胞亚群的分析和控制胸腺迁入的胸腺门控内皮细胞的发现，本项目将试图鉴定控制胸腺迁出的关键血管内皮细胞亚群。

Thymic egress of mature thymocytes is important for the establishment of peripheral T cell compartment with diversified TCR repertoire and regeneration upon accidental or therapeutic lymphoablation. While it is clear that blood vessels are involved in thymic egress, the cellular and molecular mechanisms underlying this process remain largely unknown. We recently found that endothelial lymphotoxin beta receptor (LTbR) plays a critical role for thymic egress, indicating an interesting crosstalk between LTbR ligand-expressing mature thymocytes and self-regulation of egress by mature thymocytes. In current proposed study, we will further investigate the detailed cellular and molecular mechanisms mediated by LT/LIGHT-LTbR signaling axis for thymic egress. Furthermore, we will identify the subset of thymic endothelial cells controlling thymic egress.