Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Nat Commun. 2016 Aug 5;7:12369. doi: 10.1038/ncomms12369.
Continuous thymic homing of haematopoietic progenitor cells (HPCs) via the blood is critical for normal T-cell development. However, the nature and the differentiation programme of specialized thymic endothelial cells (ECs) controlling this process remain poorly understood. Here using conditional gene-deficient mice, we find that lymphotoxin beta receptor (LTβR) directly controls thymic ECs to guide HPC homing. Interestingly, T-cell deficiency or conditional ablation of T-cell-engaged LTβR signalling results in a defect in thymic HPC homing, suggesting the feedback regulation of thymic progenitor homing by thymic products. Furthermore, we identify and characterize a special thymic portal EC population with features that guide HPC homing. LTβR is essential for the differentiation and homeostasis of these thymic portal ECs. Finally, we show that LTβR is required for T-cell regeneration on irradiation-induced thymic injury. Together, these results uncover a cellular and molecular pathway that governs thymic EC differentiation for HPC homing.
造血祖细胞（HPC）通过血液持续归巢胸腺对于正常 T 细胞发育至关重要。然而，控制这一过程的特化胸腺内皮细胞（EC）的性质和分化程序仍知之甚少。在这里，我们使用条件性基因缺陷小鼠发现，淋巴毒素β受体（LTβR）直接控制胸腺 EC 以指导 HPC 归巢。有趣的是，T 细胞缺失或条件性缺失 T 细胞激活的 LTβR 信号会导致胸腺 HPC 归巢缺陷，提示胸腺产物对胸腺祖细胞归巢的反馈调节。此外，我们鉴定并表征了具有指导 HPC 归巢特征的特殊胸腺门脉 EC 群体。LTβR 对于这些胸腺门脉 EC 的分化和稳态是必需的。最后，我们表明 LTβR 对于辐射诱导的胸腺损伤后的 T 细胞再生是必需的。总之，这些结果揭示了一条控制 HPC 归巢的胸腺 EC 分化的细胞和分子途径。
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