title: LTβR controls thymic portal endothelial cells for haematopoietic progenitor cell homing and T-cell regeneration.
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.
authors: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors: Yaoyao
authors: Y
authors: Shi
authors: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors: Weiwei
authors: W
authors: Wu
authors: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Qian
authors: Q
authors: Chai
authors: Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China.
authors: Qingqing
authors: Q
authors: Li
authors: Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China.
authors: Yu
authors: Y
authors: Hou
authors: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors: Huan
authors: H
authors: Xia
authors: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors: Boyang
authors: B
authors: Ren
authors: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Hairong
authors: H
authors: Xu
authors: School of Medicine, Tsinghua University, Beijing 100084 China.
authors: Xiaohuan
authors: X
authors: Guo
authors: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors: Caiwei
authors: C
authors: Jin
authors: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors: Mengjie
authors: M
authors: Lv
authors: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Zhongnan
authors: Z
authors: Wang
authors: Department of Pathology and Immunology, UT Southwestern Medical Center, Dallas, Texas 75235-9072, USA.
authors: Yang-Xin
authors: YX
authors: Fu
authors: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors: Mingzhao
authors: http://orcid.org/0000-0003-2001-2669
authors: M
authors: Zhu
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006706:Homeostasis; D053259:Lymphotoxin beta Receptor / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology*; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000378:metabolism
chemical_list: C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14