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New role for white blood cells in the developing brain.

Researchers led by VIB-KU Leuven discover a population of specialized brain-resident white blood cells in the mouse and human brain, and show that the presence of these lymphocytic cells is essential for normal brain development in mice. The team states these results contribute towards the increasing recognition of the role of circulating immune cells in the brain and their involvement in a range of neurological diseases.

Our onboard computer, the brain, is a sterile environment separated from the immune system by the blood-brain barrier (BBB). Consequently, this is why the brain has its own resident immune cells, known as microglia. Microglia arise in the brain during embryonic development to evolve into self-renewing cells in later development and life.

Despite this fact, overwhelming research suggests the brain is a part of the immune surveillance network covering the entire body. Despite this, it still unclear as to how the central nervous system receives intelligence from the peripheral nervous system.

A new mode of brain immunity

In addition to microglia, the brain contains sizable numbers of perivascular macrophages and dendritic cells and detectable numbers of peripheral T cells. Additionally, B cells are also present in the brain, as are natural killer cells, although whether these populations are truly brain-resident remains controversial.

Now, a study from researchers led by VIB-KU Leuven discovers a population of specialized brain-resident white blood cells in the mouse and human brain. They also show that the presence of these lymphocytic cells is essential for normal brain development in mice. The team states these results contribute towards the increasing recognition of the role of circulating immune cells in the brain and their involvement in a range of neurological diseases. The opensource study is published in the journal Cell.

Previous studies show although not widely accepted, there are a growing number of studies suggesting the immune system impacts on behavior. Unfortuately, to date, white blood cells are implicated in many different neurological disorders, including multiple sclerosis, Alzheimer’s, and Parkinson’s disease or stroke.

Notwithstanding the considerable evidence validating this statement, there is still no confirmation that resident white blood cells are also present in healthy brains. The current study demonstrates the absence of a white blood cell, called a T cell, in the brain resulted in microglia remaining suspended between a fetal and an adult developmental state. This, in turn, caused defective synaptic pruning and abnormal behavior in mice.

Neural immune cells identified

The current study utilizes a combination of imaging, single-cell, and surgical approaches to identify a CD4 T helper cell population in both the mouse and human brain, distinct from circulating CD4 T helper cells.

Results show when T helper cells are absent from the mouse brain, microglia remain suspended between a fetal and adult developmental state. This fact suggests an important role for brain-resident T cells in neurodevelopment possibly mirrored in humans. Data findings show the lack of maturation in the glia produces an excess of immature neuronal synapses and behavioral abnormalities in mice.

The lab states the brain-resident T cell population was derived through differentiation from activated circulatory cells that have reached the CNS. Subsequently, shaped by self-antigen and the microbiome before they reach the BBB. There are now multiple links between the gut microbiota and different neurological conditions without any verified explanations for what connects them that this study could clarify.

They go on to posit an interaction between circulating peripheral T helper cells and the microbiome, which is then relayed to microglia, is how the peripheral immune system communicates information to the CNS to influence behavior. They conclude the study successfully demonstrates the gut microbiome modifies white blood cells, which then traverse the BBB to act as a ‘letter to the brain’ containing vital information regarding the peripheral immune system.

Peripheral cells entering the brain

The team surmises they have identified resident white blood cells in the CNS which are normally found circulating in the peripheral immune system. For the future, the researchers state as humans have a much longer gestation than mice, questions have now arisen concerning when immune cells enter the brain to initiate the inception of microglia.

Source: VIB-KU Leuven

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