Coordination between CCR7-and CCR9-mediated chemokine signals in prevascular fetal thymus colonization
Coordination between CCR7-and CCR9-mediated chemokine signals in prevascular fetal thymus colonization
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DOI：
10.1182/blood-2006-05-024190
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发表时间：
2006-10-15
期刊：
影响因子：
20.3
通讯作者：
Takahama, Yousuke
中科院分区：
文献类型：
--
作者：
Liu, Cunlan;Saito, Fumi;Takahama, Yousuke
T淋巴祖细胞的胸腺接种是T细胞发育的先决条件。然而，指导胸腺定植的分子及其在胸腺血管化前后的作用尚不清楚。在这里，我们表明，小鼠双重缺陷的趋化因子受体CCR 7和CCR 9是有缺陷的，特别是在胎儿胸腺定植之前，但不是之后，胸腺血管化。有缺陷的血管前胎儿胸腺定殖之后是产生表皮Vy 3（+）γ δ T细胞的第一波T细胞发育的选择性丧失。出乎意料的是，CCL 21，一个CCR 7配体，不表达Foxn 1依赖的胸腺原基，但Gcm 2依赖的甲状旁腺原基，而CCL 25，一个CCR 9配体，主要是由Foxn 1依赖的胸腺原基表达，揭示了指导胎儿胸腺定植的作用，相邻的甲状旁腺。这些结果表明Gcm 2依赖性甲状旁腺和Foxn 1依赖性胸腺原基之间的协调，建立CCL 21/CCR 7-和CCL 25/CCR 9-介导的趋化因子指导血管前胎儿胸腺定殖必不可少。
Thymus seeding by T-lymphoid progenitor cells is a prerequisite for T-cell development. However, molecules guiding thymus colonization and their roles before and after thymus vascularization are unclear. Here we show that mice doubly deficient for chemokine receptors CCR7 and CCR9 were defective specifically in fetal thymus colonization before, but not after, thymus vascularization. The defective prevascular fetal thymus colonization was followed by selective loss of the first wave of T-cell development generating epidermal Vy3(+) gamma delta T cells. Unexpectedly, CCL21, a CCR7 ligand, was expressed not by Foxn1-dependent thymic primordium but by Gcm2-dependent parathyroid primordium, whereas CCL25, a CCR9 ligand, was predominantly expressed by Foxn1-dependent thymic primordium, revealing the role of the adjacent parathyroid in guiding fetal thymus colonization. These results indicate coordination between Gcm2-dependent parathyroid and Foxn1-dependent thymic primordia in establishing CCL21/CCR7- and CCL25/CCR9-mediated chemokine guidance essential for prevascular fetal thymus colonization.