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Recently, "Frontiers in Immunology" magazine published a joint research paper "Thymic Egress Is Regulated by T Cell-Derived LTβR Signal and via Distinct Thymic Portal Endothelial Cells" by Mingzhao Zhu's group and Xiaoqun Wang's group from the Institute of Biophysics, Chinese Academy of Sciences
.
The findings identified the key vascular endothelial cell subpopulations in the mouse thymus that regulate the thymic emigration of mature T cells, revealing the cellular and molecular mechanisms of thymic emigration
.
The thymus is a necessary lymphoid organ for the development of mammalian T cells.
It is the basis for the establishment of T cell adaptive immune response.
It plays a very important role in various pathological processes such as infection, tumor, and autoimmunity
.
Hematopoietic progenitor cells from bone marrow migrate to the thymus through blood circulation, which is a prerequisite for the normal development of T cells; hematopoietic progenitor cells undergo a complex development process in the thymus, differentiate into mature thymic T cells, and then migrate out of the thymus.
, Enter the peripheral circulation, establish the immune homeostasis of peripheral T cells, and perform their functions
.
It has long been recognized that the special vascular structure called "perivascular space (PVS)" located at the junction of thymic cortex and medulla is the key site for hematopoietic progenitor cell thymus homing and mature T cell thymus emigration
.
However, its cytological basis has always been an unsolved mystery in the field of immunology, which greatly limits the further development of this field.
What is more interesting is how the two types of cell migration processes that seem to be completely opposite are completed here together, and it is completely Not sure
.
In 2016, Mingzhao Zhu’s research group has undergone a large number of screening tests and has identified a group of key vascular endothelial cells that regulate the homing of hematopoietic progenitor cells, named Thymic portalendothelial cells (TPEC) (Nat Commun.
2016)
.
In this study, the researchers found that the thymus emigration of mature T cells is also located around TPEC
.
In order to explore whether these two different directions of cell migration are based on the heterogeneity of TPEC, the researchers isolated the vascular endothelial cells of the mouse thymus and performed single-cell transcriptome sequencing analysis
.
The results suggest that TPEC is indeed heterogeneous and can be further divided into two different subgroups (C2 and C6)
.
By selecting the characteristic gene BST-1 of C2, combined with the invivo cell migration function positioning test, the researchers proved that the C2 subgroup TPEC is the site of mature T cell thymus emigration, and the C6 subgroup TPEC is the home of hematopoietic progenitor cells thymus.
Location
.
Therefore, based on the previous work, the researchers further completed the identification of emigration-related thymic-gated endothelial cells (BST-1hi) and homing-related thymic-gated endothelial cells (BST-1lo/-), respectively Named eTPEC (egressTPEC) and iTPEC (immigration TPEC)
.
This study provides an important cytological basis for a complete understanding of the two basic cell migration behaviors of thymus homing and emigration
.
The researchers also further studied the developmental homeostasis of eTPEC and the cellular and molecular regulation mechanisms of mature T cell thymus emigration
.
Using a variety of knockout mice, conditional knockout mice, bone marrow chimera mice and other models, the researchers found that eTPEC development and T cell thymus emigration are affected by T cell-derived LT/LIGHT ligand Molecular and endothelial cell LTβR receptor signaling pathway regulation
.
The defect of this signaling pathway can significantly inhibit the thymic emigration of mature T cells
.
Thymus emigration is the basis for the establishment of peripheral T cell immune homeostasis and response.
Under various physiological and pathological conditions such as aging and thymus injury, the thymus emigration and immune reconstruction of mature T cells are hindered
.
The above-mentioned new discoveries about cellular and molecular mechanisms provide new ideas for further intervention in regulating the immune reconstitution of T cells
.
Xia Huan, a PhD graduate of Mingzhao Zhu's research group, and Suijuan Zhong, a doctoral graduate of Wang Xiaoqun's research group, are the co-first authors of this paper; Researcher Zhu Mingzhao and Researcher Wang Xiaoqun are the co-corresponding authors
.
The research was funded by projects from the Chinese Academy of Sciences, the Ministry of Science and Technology, and the National Natural Science Foundation of China
.
Diagram: Different subgroups of thymus-gated endothelial cells regulate thymic homing and thymus migration.
Thymic-gated endothelial cells TPEC can be further divided into two subgroups: iTPEC and eTPEC, which regulate thymic homing and maturation of hematopoietic progenitor cells, respectively The thymus of T cells migrates out
.
T cells and endothelial cells regulate the developmental homeostasis of iTPEC and eTPEC through the dialogue of the LT/LIGHT-LTβR signal axis
.
T cells provide LT/LIGHT signals to regulate thymic emigration of mature T cells
.
The endothelial cell LTβR signaling pathway regulates the thymic emigration of mature T cells
.
Links to related articles: https:// 2020 hot articles selection 1.
The cup is ready! A full paper cup of hot coffee, full of plastic particles.
.
.
2.
Scientists from the United States, Britain and Australia “Natural Medicine” further prove that the new coronavirus is a natural evolution product, or has two origins.
.
.
3.
NEJM: Intermittent fasting is right The impact of health, aging and disease 4.
Heal insomnia within one year! The study found that: to improve sleep, you may only need a heavy blanket.
5.
New Harvard study: Only 12 minutes of vigorous exercise can bring huge metabolic benefits to health.
6.
The first human intervention experiment: in nature.
"Feeling and rolling" for 28 days is enough to improve immunity.
7.
Junk food is "real rubbish"! It takes away telomere length and makes people grow old faster! 8.
Cell puzzle: you can really die if you don't sleep! But the lethal changes do not occur in the brain, but in the intestines.
.
.
9.
The super large-scale study of "Nature Communications": The level of iron in the blood is the key to health and aging! 10.
Unbelievable! Scientists reversed the "permanent" brain damage in animals overnight, and restored the old brain to a young state.
.
.
.
The findings identified the key vascular endothelial cell subpopulations in the mouse thymus that regulate the thymic emigration of mature T cells, revealing the cellular and molecular mechanisms of thymic emigration
.
The thymus is a necessary lymphoid organ for the development of mammalian T cells.
It is the basis for the establishment of T cell adaptive immune response.
It plays a very important role in various pathological processes such as infection, tumor, and autoimmunity
.
Hematopoietic progenitor cells from bone marrow migrate to the thymus through blood circulation, which is a prerequisite for the normal development of T cells; hematopoietic progenitor cells undergo a complex development process in the thymus, differentiate into mature thymic T cells, and then migrate out of the thymus.
, Enter the peripheral circulation, establish the immune homeostasis of peripheral T cells, and perform their functions
.
It has long been recognized that the special vascular structure called "perivascular space (PVS)" located at the junction of thymic cortex and medulla is the key site for hematopoietic progenitor cell thymus homing and mature T cell thymus emigration
.
However, its cytological basis has always been an unsolved mystery in the field of immunology, which greatly limits the further development of this field.
What is more interesting is how the two types of cell migration processes that seem to be completely opposite are completed here together, and it is completely Not sure
.
In 2016, Mingzhao Zhu’s research group has undergone a large number of screening tests and has identified a group of key vascular endothelial cells that regulate the homing of hematopoietic progenitor cells, named Thymic portalendothelial cells (TPEC) (Nat Commun.
2016)
.
In this study, the researchers found that the thymus emigration of mature T cells is also located around TPEC
.
In order to explore whether these two different directions of cell migration are based on the heterogeneity of TPEC, the researchers isolated the vascular endothelial cells of the mouse thymus and performed single-cell transcriptome sequencing analysis
.
The results suggest that TPEC is indeed heterogeneous and can be further divided into two different subgroups (C2 and C6)
.
By selecting the characteristic gene BST-1 of C2, combined with the invivo cell migration function positioning test, the researchers proved that the C2 subgroup TPEC is the site of mature T cell thymus emigration, and the C6 subgroup TPEC is the home of hematopoietic progenitor cells thymus.
Location
.
Therefore, based on the previous work, the researchers further completed the identification of emigration-related thymic-gated endothelial cells (BST-1hi) and homing-related thymic-gated endothelial cells (BST-1lo/-), respectively Named eTPEC (egressTPEC) and iTPEC (immigration TPEC)
.
This study provides an important cytological basis for a complete understanding of the two basic cell migration behaviors of thymus homing and emigration
.
The researchers also further studied the developmental homeostasis of eTPEC and the cellular and molecular regulation mechanisms of mature T cell thymus emigration
.
Using a variety of knockout mice, conditional knockout mice, bone marrow chimera mice and other models, the researchers found that eTPEC development and T cell thymus emigration are affected by T cell-derived LT/LIGHT ligand Molecular and endothelial cell LTβR receptor signaling pathway regulation
.
The defect of this signaling pathway can significantly inhibit the thymic emigration of mature T cells
.
Thymus emigration is the basis for the establishment of peripheral T cell immune homeostasis and response.
Under various physiological and pathological conditions such as aging and thymus injury, the thymus emigration and immune reconstruction of mature T cells are hindered
.
The above-mentioned new discoveries about cellular and molecular mechanisms provide new ideas for further intervention in regulating the immune reconstitution of T cells
.
Xia Huan, a PhD graduate of Mingzhao Zhu's research group, and Suijuan Zhong, a doctoral graduate of Wang Xiaoqun's research group, are the co-first authors of this paper; Researcher Zhu Mingzhao and Researcher Wang Xiaoqun are the co-corresponding authors
.
The research was funded by projects from the Chinese Academy of Sciences, the Ministry of Science and Technology, and the National Natural Science Foundation of China
.
Diagram: Different subgroups of thymus-gated endothelial cells regulate thymic homing and thymus migration.
Thymic-gated endothelial cells TPEC can be further divided into two subgroups: iTPEC and eTPEC, which regulate thymic homing and maturation of hematopoietic progenitor cells, respectively The thymus of T cells migrates out
.
T cells and endothelial cells regulate the developmental homeostasis of iTPEC and eTPEC through the dialogue of the LT/LIGHT-LTβR signal axis
.
T cells provide LT/LIGHT signals to regulate thymic emigration of mature T cells
.
The endothelial cell LTβR signaling pathway regulates the thymic emigration of mature T cells
.
Links to related articles: https:// 2020 hot articles selection 1.
The cup is ready! A full paper cup of hot coffee, full of plastic particles.
.
.
2.
Scientists from the United States, Britain and Australia “Natural Medicine” further prove that the new coronavirus is a natural evolution product, or has two origins.
.
.
3.
NEJM: Intermittent fasting is right The impact of health, aging and disease 4.
Heal insomnia within one year! The study found that: to improve sleep, you may only need a heavy blanket.
5.
New Harvard study: Only 12 minutes of vigorous exercise can bring huge metabolic benefits to health.
6.
The first human intervention experiment: in nature.
"Feeling and rolling" for 28 days is enough to improve immunity.
7.
Junk food is "real rubbish"! It takes away telomere length and makes people grow old faster! 8.
Cell puzzle: you can really die if you don't sleep! But the lethal changes do not occur in the brain, but in the intestines.
.
.
9.
The super large-scale study of "Nature Communications": The level of iron in the blood is the key to health and aging! 10.
Unbelievable! Scientists reversed the "permanent" brain damage in animals overnight, and restored the old brain to a young state.
.
.
