In a pioneering study, a group of international researchers has found that the brain has specific in-house immune cells that help in normal brain development and play a role in certain neurological diseases.
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The study led by Professor Adrian Liston from Babraham Institute, UK & VIB-KU Leuven, Belgium and other colleagues was published in the journal Cell.
White blood cells – sentinels of the immune system
Detailed functions of white blood cells and their types are known in different parts of the body. The brain is protected by a blood-brain-barrier or the BBB, which prevents infections and other foreign chemicals and compounds from quickly entering the brain.
The white blood cells form a part of the body’s immune system. The cells increase and trigger inflammation to fight off infection, while the BBB stops the immune cells from entering the brain.
The brain has its own immune system sentinel cells called the microglial cells. If the microglial cells become damaged, they increase, trigger inflammation and repair the damaged tissues.
Where do these microglial cells come from?
Studies have shown that during embryonic development, the microglial cells enter and stay in the brain. Their population remains constant as they self-renew during the lifetime of the brain.
White blood cells in brain – what is known?
Several studies have revealed that there is a role of white blood cells in certain neurological diseases such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and cerebrovascular accident or stroke.
The researchers explained that there has been no scientific evidence showing the presence of these white blood cells in healthy brains. Therefore, the presence of these cells in a healthy brain has remained controversial.
What was this study about?
This study was a collaborative effort from a team of researchers led by Prof. Adrian Liston. The group sought to clarify the presence and role of white blood cells in developing brains of mice and humans.
A misconception about white blood cells comes from their name.” These cells are not limited to the bloodstream, he said. He added, “These 'immune cells' are not just present in the blood. They are constantly circulating around our body and enter all of our organs, including - as it turns out - the brain. We are only just starting to discover what white blood cells do when they leave the blood. This research indicates that they act as a go between, transferring information from the rest of the body to the brain environment.”
Dr Oliver Burton, Babraham Institute
What was done?
For this study, the team studied brain tissues of mice and humans in their labs, looking for a specific type of white blood cells called the T cells.
These T cells are activated when infective microbes are present on cell surfaces, and can trigger an inflammatory and immune response when an infective agent is detected.
There are two main types of T cells – the helper T cells and the killer T cells. In this study, the researchers studied how the T cells entered the brain and how they developed exclusive features that made them brain-resident T cells.
According to Dr. Carlos Roca, co-author of the study from Babraham Institute, “Science is becoming increasingly multidisciplinary. Here, we didn't just bring in expertise from immunology, neuroscience and microbiology, but also from computer science and applied mathematics. New approaches for data analysis allow us to reach a much deeper level of understanding of the biology of the white blood cells we found in the brain.”
What did they find?
This study quantified the population of T cells in the brain tissues of mice and humans. These were found to be resident T cells in the brain tissues – distinct from what was found elsewhere in the body.
The team showed that the microglial cells, which were supposed to act as immune cells in the brain, did not develop entirely if the T cells were absent in a mice’s brain. Their features were arrested between fetal and adult stages, the researchers noted. Therefore, these resident T cells were found to play a role in the development of microglial cells in the brain.
The mice that did not have brain T cells also showed behavioral changes, proving that T cells play an essential role in brain development.
In mice, the wave of entry of immune cells at birth triggers a switch in brain development. Humans have a much longer gestation than mice though, and we don't know about the timing of immune cell entry into the brain. Does this occur before birth? Is it delayed until after birth? Did a change in timing of entry contribute to the evolution of enhanced cognitive capacity in humans?”
Professor Liston
Implications of the study findings
Dr. Emanuela Pasciuto, a co-author of the study from VIB-KU Leuven, said, “It has been really exciting to work on this project. We are learning so much about how our immune system can alter our brain, and how our brain modifies our immune system. The two are far more interconnected than we previously thought.”
Liston adds that there also seems to be a role played by gut microbes. He added, “There are now multiple links between the bacteria in our gut and different neurological conditions, but without any convincing explanations for what connects them. We show that white blood cells are modified by gut bacteria, and then take that information with them into the brain. This could be the route by which our gut microbiome influences the brain.”
Researchers conclude that if the role of these immune cells is known in the healthy brain, more could be understood about their role in neurological and neurodegenerative progressive diseases such as Alzheimer’s, multiple sclerosis and Parkinson’s disease.
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