JEM:树突细胞S1P裂解酶调节T细胞从胸腺释放到血液中

Dendritic cell sphingosine-1-phosphate lyase regulates thymic egress

在一项新的研究中，来自美国加州大学旧金山分校奥克兰贝尼奥夫儿童医院的Julie Saba博士及其团队揭示出胸腺树突细胞的一种新作用。这可能导致人们开发出治疗自身免疫疾病、免疫缺陷、早熟、感染、癌症和骨髓移植后的免疫缺乏等疾病的新策略。

T cell egress from the thymus is essential for adaptive immunity and involves chemotaxis along a sphingosine-1-phosphate (S1P) gradient. Pericytes at the corticomedullary junction produce the S1P egress signal, whereas thymic parenchymal S1P levels are kept low through S1P lyase (SPL)-mediated metabolism. Although SPL is robustly expressed in thymic epithelial cells (TECs), in this study, we show that deleting SPL in CD11c+ dendritic cells (DCs), rather than TECs or other stromal cells, disrupts the S1P gradient, preventing egress. Adoptive transfer of peripheral wild-type DCs rescued the egress phenotype of DC-specific SPL knockout mice. These studies identify DCs as metabolic gatekeepers of thymic egress. Combined with their role as mediators of central tolerance, DCs are thus poised to provide homeostatic regulation of thymic export.