LTβR controls thymic portal endothelial cells for haematopoietic progenitor cell homing and T-cell regeneration

Yaoyao Shi, Weiwei Wu, Qian Chai, Qingqing Li, Yu Hou, Huan Xia, Boyang Ren, Hairong Xu, Xiaohuan Guo, Caiwei Jin, Mengjie Lv, Zhongnan Wang, Yang Xin Fu, Mingzhao Zhu

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Article number12369
JournalNature Communications
Volume7
DOIs
StatePublished - Aug 5 2016

Fingerprint

Lymphotoxin beta Receptor
homing
T-cells
Endothelial cells
Hematopoietic Stem Cells
regeneration
Regeneration
Endothelial Cells
T-Lymphocytes
cells
homeostasis
Ablation
Cell Differentiation
Homeostasis
Blood
genes
Genes
ablation
blood
mice

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

LTβR controls thymic portal endothelial cells for haematopoietic progenitor cell homing and T-cell regeneration. / Shi, Yaoyao; Wu, Weiwei; Chai, Qian; Li, Qingqing; Hou, Yu; Xia, Huan; Ren, Boyang; Xu, Hairong; Guo, Xiaohuan; Jin, Caiwei; Lv, Mengjie; Wang, Zhongnan; Fu, Yang Xin; Zhu, Mingzhao.

In: Nature Communications, Vol. 7, 12369, 05.08.2016.

Research output: Contribution to journalArticle

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 2016, 'LTβR controls thymic portal endothelial cells for haematopoietic progenitor cell homing and T-cell regeneration', Nature Communications, vol. 7, 12369. https://doi.org/10.1038/ncomms12369
Shi, Yaoyao ; Wu, Weiwei ; Chai, Qian ; Li, Qingqing ; Hou, Yu ; Xia, Huan ; Ren, Boyang ; Xu, Hairong ; Guo, Xiaohuan ; Jin, Caiwei ; Lv, Mengjie ; Wang, Zhongnan ; Fu, Yang Xin ; Zhu, Mingzhao. / LTβR controls thymic portal endothelial cells for haematopoietic progenitor cell homing and T-cell regeneration. In: Nature Communications. 2016 ; Vol. 7.
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abstract = "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.",
author = "Yaoyao Shi and Weiwei Wu and Qian Chai and Qingqing Li and Yu Hou and Huan Xia and Boyang Ren and Hairong Xu and Xiaohuan Guo and Caiwei Jin and Mengjie Lv and Zhongnan Wang and Fu, {Yang Xin} and Mingzhao Zhu",
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AU - Hou, Yu

AU - Xia, Huan

AU - Ren, Boyang

AU - Xu, Hairong

AU - Guo, Xiaohuan

AU - Jin, Caiwei

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AU - Wang, Zhongnan

AU - Fu, Yang Xin

AU - Zhu, Mingzhao

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