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The brain is often referred to as the commander of the whole body. In order to protect this vital organ from microbial infections or other toxic substances, the abundant blood vessels form a barrier between the brain parenchyma and the blood. The blood-brain barrier, which is mainly composed of blood vessel cells, strictly filters the substances entering the brain from the blood, thereby ensuring that the brain is in a relatively stable and safe environment.
At the same time, microglia stationed in brain tissue, as innate immune cells, "monitor" the environment of the brain parenchyma, identify and engulf pathogens, etc., and build a line of defense to protect the brain.
Image credit: 123RF
And among the immune defenses that protect the brain, there is another important new member that has only recently become known. In a recent research paper published in the top academic journal Nature, researchers from Kyushu University in Japan and the University of Freiburg in Germany have studied another type of innate immune cells throughout the brain, revealing for the first time how they form and enhance important functions such as the blood-brain barrier.
The researchers point out that a detailed analysis of these special immune cells is expected to elucidate the mechanism of brain development, as well as the pathogenesis and treatment direction of various brain diseases.
The immune cells that the study focused on are macrophages, like microglia. But unlike microglia, which are distributed in the brain parenchyma, these macrophages are located in the meninges, around blood vessels, and other parts of the brain that surround the brain.
Using cutting-edge single-cell analysis techniques, cell fate tracking techniques, and cell-specific transgenic mouse models, the researchers labeled different types of brain macrophages and their progenitor cells in this study, confirming that these special macrophages distributed in the meninges, blood vessels, and other parts have common progenitors with microglia in the embryonic stage.
Microscopic images show macrophages in different tissues in mouse brains (Credit: Medical Center—University of Freiburg/Dr. Lukas Amann)
However, although the precursor cells were in place in the brain early, these special macrophages matured later than expected. The researchers confirmed the level of maturity of individual cells by examining their gene activity.
"We found that these immune cells migrate from the meninges to the cerebral blood vessels shortly before birth and mature there. The process does not complete until about a few weeks after birth. Professor Marco Prinz, co-corresponding author of the study, noted that "the brain is fragile at the beginning of life, and I think that's part of the reason." ”
Further studies have shown that these special brain macrophages do not mature until after birth because vascular smooth muscle cells provide important signals.
Schematic diagram of different development trajectories of perivascular macrophages (pvMΦ), meningeal macrophages (mMΦ) and microglia (Image source: Reference[1])
"In addition to the blood-brain barrier, these immune cells we studied also control what can reach brain cells from the bloodstream, they swallow pathogens and prevent excessive inflammation, and they are also involved in the development of cancer, Alzheimer's disease and multiple sclerosis." Professor Prinz added.
The researchers believe that as the understanding of these brain immune cells gradually deepens, there will be a new understanding to better understand the pathogenesis of these diseases, and there will be opportunities to develop new therapies that target the cells on this basis.
Resources:
[2] New discoveries about the origin of the brain's immune system. Retrieved Apr. 24, 2022 from https://medicalxpress.com/news/2022-04-discoveries-brain-immune.html
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