New role for white blood cells in the developing brain
The presence of white blood cells is essential for normal brain
development in mice

Date:
July 22, 2020
Source:
Babraham Institute
Summary:
Whether white blood cells can be found in the brain has been
controversial, and their role there a complete mystery. Scientists
describe a population of specialized brain-resident immune cells
discovered in the mouse and human brain, and show that the presence
of white blood cells is essential for normal brain development
in mice.



FULL STORY ========================================================================== Whether white blood cells can be found in the brain has been
controversial, and their role there a complete mystery. In a study
published in Cell, an international team of scientists led by Professor
Adrian Liston (Babraham Institute, UK & VIB-KU Leuven, Belgium) describe
a population of specialised brain-resident immune cells discovered in
the mouse and human brain, and show that the presence of white blood
cells is essential for normal brain development in mice.


==========================================================================
Like a highly fortified headquarters, our brain enjoys special protection
from what is circulating in the rest of our body through the blood-brain barrier.

This highly selective border makes sure that passage from the blood to
the brain is tightly regulated.

The blood-brain barrier also separates the brain from our body's
immune system, which is why it has its own resident immune cells, called microglia, which trigger inflammation and tissue repair. Microglia arrive
in the brain during embryonic development, and later on, the population
becomes self-renewing.

Yet, white blood cells -- which are part of our immune system -- have been found to play a role in different brain diseases, including multiple
sclerosis, Alzheimer's and Parkinson's disease or stroke. Whether
or not white blood cells can be found in healthy brains as well, and
what they might be doing there, has been subject of intense debate. An interdisciplinary team of scientists led by Prof. Adrian Liston (Babraham Institute and VIB-KU Leuven) set out to find the answers.

White blood cells in the brain "A misconception about white blood
cells comes from their name," explains Dr Oliver Burton (Babraham
Institute). "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" The team quantified
and characterised a small but distinct population of brain- resident
T helper cells present in mouse and human brain tissue. T cells are
a specific type of white blood cells specialized for scanning cell
surfaces for evidence of infection and triggering an appropriate immune response. New technologies allowed the researchers to study the cells in
great detail, including the processes by which circulating T cells entered
the brain and began to develop the features of brain-resident T cells.



==========================================================================
Dr Carlos Roca (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." An evolutionary role When T helper
cells are absent from the brain, the scientists found that the resident
immune cells -- microglia -- in the mouse brain remained suspended
between a fetal and adult developmental state. Observationally, mice
lacking brain T cells showed multiple changes in their behavior. The
analysis points to an important role for brain-resident T cells in
brain development. If T cells participate in normal brain development
in mice, could the same be true in humans? "In mice, the wave of entry
of immune cells at birth triggers a switch in brain development," says
Liston. "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?" The findings open up a whole new range
of questions about how the brain and our immune system interact. "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," says Dr Emanuela Pasciuto
(VIB-KU Leuven).

The study also brings in a connection with the gut microbiome, says
Liston: "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." Taken together, the results contribute towards
the increasing recognition of the role of immune cells in the brain and
shed new light on its involvement in a range of neurological diseases.


========================================================================== Story Source: Materials provided by Babraham_Institute. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Emanuela Pasciuto, Oliver T. Burton, Carlos P. Roca, Vasiliki Lagou,
Wenson D. Rajan, Tom Theys, Renzo Mancuso, Raul Y. Tito, Lubna
Kouser, Zsuzsanna Callaerts-Vegh, Alerie G. de la Fuente, Teresa
Prezzemolo, Loriana G. Mascali, Aleksandra Brajic, Carly E. Whyte,
Lidia Yshii, Anna Martinez-Muriana, Michelle Naughton, Andrew Young,
Alena Moudra, Pierre Lemaitre, Suresh Poovathingal, Jeroen Raes,
Bart De Strooper, Denise C.

Fitzgerald, James Dooley, Adrian Liston. Microglia Require CD4 T
Cells to Complete the Fetal-to-Adult Transition. Cell, 2020; DOI:
10.1016/ j.cell.2020.06.026 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200722112659.htm

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