Nature Communications 7, Article number: 12369 doi:10.1038/ncomms12369, Received 22 December 2015 Accepted 27 June 2016 Published 05 August 2016
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
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.
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文章链接：http://www.nature.com/ncomms/2016/160805/ncomms12369/full/ncomms12369.html
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