LTβR controls thymic portal endothelial cells for haematopoietic progenitor cell homing and T-cell regeneration
نویسندگان
چکیده
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.
منابع مشابه
Lymphotoxin β Receptor Controls T Cell Progenitor Entry to the Thymus
The recruitment of lymphoid progenitors to the thymus is essential to sustain T cell production throughout life. Importantly, it also limits T lineage regeneration following bone marrow transplantation, and so contributes to the secondary immunodeficiency that is caused by delayed immune reconstitution. Despite this significance, the mechanisms that control thymus colonization are poorly unders...
متن کاملStrategies to Improve Homing of Stem Cells to achieve better Efficacy in Stem Cell Therapy
Stem/progenitor cell based therapeutic approach in our daily routine clinical practice, has been elusive dream in medical sciences and improvement of stem cell homing as one of major challenges in cell therapy programs, has been considered a promising milestone. It has been proved that stem/progenitor cells exhibit a homing response to injured tissues/organs, mediated by interactions of chemoki...
متن کاملEpithelial LTβR signaling controls the population size of the progenitors of medullary thymic epithelial cells in neonatal mice
The establishment of T cell central tolerance critically relies on the development and maintenance of the medullary thymic epithelial cells (mTECs). Disrupted signaling of lymphotoxin beta receptor (LTβR) results in dramatically reduced mTEC population. However, whether LTβR directly or indirectly control mTECs remains undetermined; how LTβR controls this process also remain unclear. In this st...
متن کاملLooking for immortality: Review of phytotherapy for stem cell senescence
Objective(s): In this paper, we discussed natural agents with protective effects against stem cell senescence. Different complications have been observed due to stem cell senescence and the most important of them is “Aging”. Senescent cells have not normal function and their secretary inflammatory factors induce chronic inflammation in body which causes different patho...
متن کامل