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Written | November Responsible Editor | Enzyme Meninges is a membranous structure that wraps the central nervous system.
The central nervous system is rich in immune cells and mediates the immune surveillance process of the central nervous system
.
Everyone has always believed that the immune cells in the central nervous system mainly come from the blood circulatory system
.
Myeloid cells include monocytes, neutrophils and macrophages, and show different heterogeneity and different functions according to their ontogeny and local niches [1]
.
However, there have been few studies on the source and role of monocytes, macrophages and neutrophils residing at the borders of the brain in homeostasis and central nervous system dysfunction
.
(Picture source paper 2) To this end, the Jonathan Kipnis research group of the Johannes Gutenberg University Medical Center in Mainz, Germany, published an article titled Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma in Science, which was unveiled The skull and vertebral bone marrow function as a reservoir of myeloid cells in the parenchyma of the meninges and central nervous system, breaking the traditional view that the source of these myeloid cells in the process of inflammation is blood
.
Science also published an online paper from the Marco Colonna Research Group at the University of Washington School of Medicine, titled: Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders
.
They used single-cell sequencing and other methods to reveal that meningeal B cells can be derived from the cranial bone marrow, confirming the diverse sources of central nervous system immune cells
.
The following focuses on the interpretation of the first paper: In order to find the source of the marginal myeloid cells of the central nervous system, the authors connected the circulatory systems of UBC-GFP wild-type mice through surgery
.
60 days after the surgical connection, the authors performed flow cytometry on blood, brain-related tissues (dura and spinal dura mater), hematopoietic organs (cranial bone marrow, vertebral bone marrow, femoral bone marrow) and peripheral blood control tissues (spleen and liver) Cell sorting analysis (Figure 1)
.
After sorting, the authors found that the number of GFP+ B cells in the chimera was extremely small at the edge of the brain, which suggested that these cells may not be of blood origin
.
Figure 1 The wild-type and UBC-GFP mice were surgically connected and the chimera composition was analyzed by cell sorting.
After discovering this phenomenon, the authors wanted to know the source of these myeloid cells at the edge of the brain
.
The skull and the dura are directly connected by ossified vascular channels, extending from the bone marrow to the central nervous system, which will cause neutrophils and tumor cells to migrate under inflammation or pathological conditions [2]
.
The authors found that the use of AMD3100, an antagonist of CXCR4, would make the mouse skull thin and exposed, which would promote the excretion of myeloid cells
.
This resulted in a significant increase in the ratio of monocytes and neutrophils in the dura, but the addition of this antagonist did not change the ratio of blood, lung or other bone marrow niches
.
This result indicates that myeloid cells have migrated directly from the local skull bone marrow
.
This result prompted the authors to confirm in detail that the skull bone marrow may be the reservoir of meningeal myeloid cells
.
Therefore, the authors developed a skull flap transplantation experiment (Figure 2).
A skull containing a large amount of bone marrow reserves was transplanted from UBC-GFP mice to cover the same size skull window created in wild-type mice
.
It should be noted that the dura mater of these mice was carefully preserved intact
.
The authors found that after returning to steady-state conditions after surgery, the cell niches of myeloid cells distributed along the border of the brain receive a large amount of input from the bone marrow of the skull, which seems to be the key distributor of myeloid cells
.
The results of this experiment provide examples of healthy tissues that also contain myeloid cells, and the myeloid cells are continuously supplemented by sources other than blood
.
Figure 2 Meningeal transplantation in mice.
Because a large number of non-blood-derived monocytes and neutrophils are stored in the dura, the authors speculate that these cells may act as a rapid response myeloid cell reservoir in the event of central nervous system injury
.
To prove this point, the authors constructed three models of central nervous system injury, including experimental autoimmune myelitis, spinal cord injury, and optic nerve crush injury
.
Through single-cell sequencing analysis, the authors found that these monocytes and neutrophils are indeed a myeloid cell bank located at the border of the central nervous system, and have significantly different routing characteristics from immune cells in the blood
.
The reservoir is ready for defense under steady-state conditions, replenishing blood-borne inflammatory cells to support the central nervous system
.
In summary, the authors found that the meninges surrounding the central nervous system contain a pool of myeloid cells containing monocytes and neutrophils.
These cells are not derived from the blood in the previous Van Furth's classic view
.
These findings are for nerve damage and the infiltration of immune cells into the nervous system during autoimmune processes, and may provide guidance for possible future treatments using meningeal immune cells.
.
Original link: https://science.
sciencemag.
org/content/early/2021/06/02/science.
abf7844 https://science.
sciencemag.
org/content/early/2021/06/02/science.
abf9277 ：11 References 1.
Guilliams, M.
, Mildner, A.
& Yona, S.
Developmental and Functional Heterogeneity of Monocytes.
Immunity 49, 595-613, doi:10.
1016/j.
immuni.
2018.
10.
005 (2018).
2.
Cai, R.
et al.
Panoptic imaging of transparent mice reveals whole-body neuronal projections and skull-meninges connections.
Nature neuroscience 22, 317-327, doi:10.
1038/s41593-018-0301-3 (2019).
Reprinted Note [Original Articles] BioArt original articles are welcome to be shared by individuals.
Reprinting is prohibited without permission.
The copyrights of all published works are owned by BioArt
.
BioArt reserves all statutory rights and offenders must be investigated
.
The central nervous system is rich in immune cells and mediates the immune surveillance process of the central nervous system
.
Everyone has always believed that the immune cells in the central nervous system mainly come from the blood circulatory system
.
Myeloid cells include monocytes, neutrophils and macrophages, and show different heterogeneity and different functions according to their ontogeny and local niches [1]
.
However, there have been few studies on the source and role of monocytes, macrophages and neutrophils residing at the borders of the brain in homeostasis and central nervous system dysfunction
.
(Picture source paper 2) To this end, the Jonathan Kipnis research group of the Johannes Gutenberg University Medical Center in Mainz, Germany, published an article titled Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma in Science, which was unveiled The skull and vertebral bone marrow function as a reservoir of myeloid cells in the parenchyma of the meninges and central nervous system, breaking the traditional view that the source of these myeloid cells in the process of inflammation is blood
.
Science also published an online paper from the Marco Colonna Research Group at the University of Washington School of Medicine, titled: Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders
.
They used single-cell sequencing and other methods to reveal that meningeal B cells can be derived from the cranial bone marrow, confirming the diverse sources of central nervous system immune cells
.
The following focuses on the interpretation of the first paper: In order to find the source of the marginal myeloid cells of the central nervous system, the authors connected the circulatory systems of UBC-GFP wild-type mice through surgery
.
60 days after the surgical connection, the authors performed flow cytometry on blood, brain-related tissues (dura and spinal dura mater), hematopoietic organs (cranial bone marrow, vertebral bone marrow, femoral bone marrow) and peripheral blood control tissues (spleen and liver) Cell sorting analysis (Figure 1)
.
After sorting, the authors found that the number of GFP+ B cells in the chimera was extremely small at the edge of the brain, which suggested that these cells may not be of blood origin
.
Figure 1 The wild-type and UBC-GFP mice were surgically connected and the chimera composition was analyzed by cell sorting.
After discovering this phenomenon, the authors wanted to know the source of these myeloid cells at the edge of the brain
.
The skull and the dura are directly connected by ossified vascular channels, extending from the bone marrow to the central nervous system, which will cause neutrophils and tumor cells to migrate under inflammation or pathological conditions [2]
.
The authors found that the use of AMD3100, an antagonist of CXCR4, would make the mouse skull thin and exposed, which would promote the excretion of myeloid cells
.
This resulted in a significant increase in the ratio of monocytes and neutrophils in the dura, but the addition of this antagonist did not change the ratio of blood, lung or other bone marrow niches
.
This result indicates that myeloid cells have migrated directly from the local skull bone marrow
.
This result prompted the authors to confirm in detail that the skull bone marrow may be the reservoir of meningeal myeloid cells
.
Therefore, the authors developed a skull flap transplantation experiment (Figure 2).
A skull containing a large amount of bone marrow reserves was transplanted from UBC-GFP mice to cover the same size skull window created in wild-type mice
.
It should be noted that the dura mater of these mice was carefully preserved intact
.
The authors found that after returning to steady-state conditions after surgery, the cell niches of myeloid cells distributed along the border of the brain receive a large amount of input from the bone marrow of the skull, which seems to be the key distributor of myeloid cells
.
The results of this experiment provide examples of healthy tissues that also contain myeloid cells, and the myeloid cells are continuously supplemented by sources other than blood
.
Figure 2 Meningeal transplantation in mice.
Because a large number of non-blood-derived monocytes and neutrophils are stored in the dura, the authors speculate that these cells may act as a rapid response myeloid cell reservoir in the event of central nervous system injury
.
To prove this point, the authors constructed three models of central nervous system injury, including experimental autoimmune myelitis, spinal cord injury, and optic nerve crush injury
.
Through single-cell sequencing analysis, the authors found that these monocytes and neutrophils are indeed a myeloid cell bank located at the border of the central nervous system, and have significantly different routing characteristics from immune cells in the blood
.
The reservoir is ready for defense under steady-state conditions, replenishing blood-borne inflammatory cells to support the central nervous system
.
In summary, the authors found that the meninges surrounding the central nervous system contain a pool of myeloid cells containing monocytes and neutrophils.
These cells are not derived from the blood in the previous Van Furth's classic view
.
These findings are for nerve damage and the infiltration of immune cells into the nervous system during autoimmune processes, and may provide guidance for possible future treatments using meningeal immune cells.
.
Original link: https://science.
sciencemag.
org/content/early/2021/06/02/science.
abf7844 https://science.
sciencemag.
org/content/early/2021/06/02/science.
abf9277 ：11 References 1.
Guilliams, M.
, Mildner, A.
& Yona, S.
Developmental and Functional Heterogeneity of Monocytes.
Immunity 49, 595-613, doi:10.
1016/j.
immuni.
2018.
10.
005 (2018).
2.
Cai, R.
et al.
Panoptic imaging of transparent mice reveals whole-body neuronal projections and skull-meninges connections.
Nature neuroscience 22, 317-327, doi:10.
1038/s41593-018-0301-3 (2019).
Reprinted Note [Original Articles] BioArt original articles are welcome to be shared by individuals.
Reprinting is prohibited without permission.
The copyrights of all published works are owned by BioArt
.
BioArt reserves all statutory rights and offenders must be investigated
.
