Critical role for CXCR4 signaling in progenitor localization and T cell differentiation in the postnatal thymus
Critical role for CXCR4 signaling in progenitor localization and T cell differentiation in the postnatal thymus
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DOI：
10.4049/jimmunol.171.9.4521
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发表时间：
2003-11-01
影响因子：
4.4
通讯作者：
Petrie, HT
中科院分区：
文献类型：
--
作者：
Plotkin, J;Prockop, SE;Petrie, HT
胸腺中的T细胞分化依赖于皮质离散区域中淋巴祖细胞和基质细胞之间的顺序相互作用。在这里，我们表明CXCL 12/CXCR 4信号传导对于早期祖细胞正确定位到皮质中以及成功的稳态分化是绝对必要的。胸腺中的所有早期祖细胞都表达CXCR 4，其配体（CXCL 12）仅在皮质中的基质细胞中表达，早期祖细胞在体外响应CXCL 12而迁移，而体内胸腺特异性CXCR 4缺失导致皮质定位失败和发育停滞。这些发现表明CXCR 4在促进早期淋巴祖细胞定位于胸腺组织区域中的关键和非冗余作用，在胸腺组织区域中控制谱系定型和增殖。
T cell differentiation in the thymus depends on sequential interactions between lymphoid progenitors and stromal cells in discrete regions of the cortex. Here we show that CXCL12/CXCR4 signaling is absolutely required for proper localization of early progenitors into the cortex and thus for successful steady state differentiation. All early progenitors in the thymus express CXCR4, and its ligand (CXCL12) is expressed only by stromal cells in the cortex, where early progenitors are found. Early progenitors migrate in response to CXCL12 in vitro, while thymus-specific deletion of CXCR4 in vivo results in failed cortical localization and developmental arrest. These findings indicate a crucial and nonredundant role for CXCR4 in facilitating localization of early lymphoid progenitors to tissue regions of the thymus, where lineage commitment and proliferation are controlled.