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 and Mingzhao Zhu ()
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Yaoyao Shi: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences
Weiwei Wu: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences
Qian Chai: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences
Qingqing Li: Biodynamic Optical Imaging Center, College of Life Sciences, Peking University
Yu Hou: Biodynamic Optical Imaging Center, College of Life Sciences, Peking University
Huan Xia: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences
Boyang Ren: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences
Hairong Xu: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences
Xiaohuan Guo: School of Medicine, Tsinghua University
Caiwei Jin: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences
Mengjie Lv: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences
Zhongnan Wang: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences
Yang-Xin Fu: UT Southwestern Medical Center
Mingzhao Zhu: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms12369

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