LTβR controls thymic portal endothelial cells for haematopoietic progenitor cell homing and T-cell regeneration.
LTβR controls thymic portal endothelial cells for haematopoietic progenitor cell homing and T-cell regeneration.
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LT beta R 控制胸腺门脉内皮细胞，促进造血祖细胞归巢和 T 细胞再生
DOI：
10.1038/ncomms12369
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发表时间：
2016-08-05
影响因子：
16.6
通讯作者：
Zhu M
中科院分区：
文献类型：
--
作者：
Shi Y;Wu W;Chai Q;Li Q;Hou Y;Xia H;Ren B;Xu H;Guo X;Jin C;Lv M;Wang Z;Fu YX;Zhu M
造血祖细胞（HPCs）通过血液持续的胸腺归巢对正常的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（ECs）的性质和分化程序仍然知之甚少。在条件基因缺陷小鼠中，我们发现淋巴毒素β受体（LTβR）直接控制胸腺ECs引导HPC归巢。有趣的是，t细胞缺乏或t细胞参与的LTβR信号的条件消融导致胸腺HPC归巢缺陷，提示胸腺产物对胸腺祖归巢的反馈调节。此外，我们确定并描述了一种特殊的胸腺门户EC种群，其特征指导HPC归巢。LTβR对这些胸腺门脉ECs的分化和稳态至关重要。最后，我们发现LTβR是辐射诱导胸腺损伤的t细胞再生所必需的。总之，这些结果揭示了控制胸腺EC分化的HPC归巢的细胞和分子途径。淋巴祖细胞从骨髓迁移到胸腺，产生T和NK细胞系。在这里，作者描述了一个淋巴素受体β依赖胸腺内皮细胞群，它引导淋巴祖细胞在胸腺内归巢。
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. Lymphoid progenitors migrate from the bone marrow into the thymus to give rise to T and NK cell lineages. Here the authors characterize a lymphotoxin receptor beta-dependent population of thymic endothelial cells that guide lymphoid progenitor homing in the thymus.