Thymic Egress Is Regulated by T Cell-Derived LTβR Signal and via Distinct Thymic Portal Endothelial Cells.
Thymic Egress Is Regulated by T Cell-Derived LTβR Signal and via Distinct Thymic Portal Endothelial Cells.
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胸腺出口由 T 细胞衍生的 LTβR 信号和独特的胸腺门脉内皮细胞调节
DOI：
10.3389/fimmu.2021.707404
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发表时间：
2021
影响因子：
7.3
通讯作者：
Zhu M
中科院分区：
文献类型：
--
作者：
Xia H;Zhong S;Zhao Y;Ren B;Wang Z;Shi Y;Chai Q;Wang X;Zhu M
血管周围间隙（PVS）的胸腺血管是造血祖细胞（HPC）归巢和成熟胸腺细胞流出的关键部位。有趣的是，不同的相反的迁移如何在同一个地方发生。与PVS相关的特化胸腺门静脉内皮细胞（TPEC）的一个子集已被鉴定为HPC的进入位点。然而，成熟胸腺细胞的细胞基础和机制尚未得到很好的定义。在本研究中，我们使用各种常规和条件性基因缺陷小鼠模型，首次证实了内皮细胞光敏素β受体（LTβR）在胸腺排出中的作用，并排除了来自上皮细胞或树突状细胞的LTβR的作用。此外，我们发现，T细胞衍生的配体光敏素（LT）和光是胸腺出口所需的，这表明T细胞和内皮细胞（EC）之间的串扰胸腺出口控制。此外，免疫荧光染色分析有趣地显示TPEC也是成熟胸腺细胞的出口位点。胸腺内皮细胞的单细胞转录组学分析表明，TPEC是异质性的，并且可以根据BST-1表达水平进一步分为两个亚群。重要的是，BST-1hi群体与胸腺细胞流出相关，而BST-1 lo/−群体与HPC沉降相关。因此，我们定义了一个LT/LIGHT-LTβR信号介导的细胞串扰调节胸腺出口，并分别揭示了控制胸腺归巢和出口的TPEC的不同子集。
Thymic blood vessels at the perivascular space (PVS) are the critical site for both homing of hematopoietic progenitor cells (HPCs) and egress of mature thymocytes. It has been intriguing how different opposite migrations can happen in the same place. A subset of specialized thymic portal endothelial cells (TPECs) associated with PVS has been identified to function as the entry site for HPCs. However, the cellular basis and mechanism underlying egress of mature thymocytes has not been well defined. In this study, using various conventional and conditional gene-deficient mouse models, we first confirmed the role of endothelial lymphotoxin beta receptor (LTβR) for thymic egress and ruled out the role of LTβR from epithelial cells or dendritic cells. In addition, we found that T cell-derived ligands lymphotoxin (LT) and LIGHT are required for thymic egress, suggesting a crosstalk between T cells and endothelial cells (ECs) for thymic egress control. Furthermore, immunofluorescence staining analysis interestingly showed that TPECs are also the exit site for mature thymocytes. Single-cell transcriptomic analysis of thymic endothelial cells suggested that TPECs are heterogeneous and can be further divided into two subsets depending on BST-1 expression level. Importantly, BST-1hi population is associated with thymic egressing thymocytes while BST-1lo/− population is associated with HPC settling. Thus, we have defined a LT/LIGHT-LTβR signaling–mediated cellular crosstalk regulating thymic egress and uncovered distinct subsets of TPECs controlling thymic homing and egress, respectively.
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影响因子：
5.5
作者：
James KD;Jenkinson WE;Anderson G
通讯作者：
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影响因子：
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作者：
Nagatake T;Zhao YC;Ito T;Itoh M;Kometani K;Furuse M;Saika A;Node E;Kunisawa J;Minato N;Hamazaki Y
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影响因子：
4.4
作者：
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通讯作者：
Amagai, Takashi
影响因子：
32.4
作者：
Kabashima, K;Banks, TA;Cyster, JG
通讯作者：
Cyster, JG
DOI：
10.1084/jem.20121462
发表时间：
2013-03-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Onder L;Danuser R;Scandella E;Firner S;Chai Q;Hehlgans T;Stein JV;Ludewig B
通讯作者：
Ludewig B