The skull is a reservoir of unexpected cerebral immunity

The immune system is the best frenemy of the brain. It protects the brain from infections and helps heal damaged tissue, but it causes inflammation that causes autoimmune diseases and neurodegeneration.

Two new studies in mice suggest that the double-edged nature of the immune system-brain relationship may result in the origin of immune cells that orbit the meninges, the tissue that surrounds the brain and spinal cord. I am. In a complementary study published in the journal on June 3 ScienceTwo researchers at the University of Washington School of Medicine in St. Louis unexpectedly discovered that many of the immune cells in the meninges originate from the bone marrow of the skull and travel through special pathways to the brain without blood. Did.

These skull-derived immune cells are peacekeepers and are dedicated to staying healthy. It is the other immune cells that arrive from the bloodstream that are causing the problem. They have genetic characteristics that indicate that they may promote autoimmunity and inflammation and become more abundant under conditions of aging, illness and injury. It reveals an important aspect of the connection between the immune systems, which may help us to understand a wide range of brain disorders.

“Our knowledge had this gap that applies to almost all neurological disorders, such as neuro-COVID, Alzheimer’s disease, multiple sclerosis, and brain damage,” said Dr. Jonathan Kipnis, Alan A. And Edith L. Wolff said. Special Professor of Pathology and Immunology and BJC Researcher. Kipnis is the senior author of one of the treatises. “I knew that immune cells were involved in the neurological state, but where did they come from? What we found was that these cells had never been described before. There is a new cause. “

Earlier this year, Kipnis showed that immune cells located in the meninges monitor the brain. As part of these new studies, Kipnis and Marco Colonna, MD, Robert Locke Veriview, MD, professor of pathology, and the lead author of another paper will find out where such cells came from. I launched my own project. Kipnis focused on the congenital arm of the immune system, and Colonna focused on the adaptive arm. Innate immune cells are the cause of inflammation and help protect against infection and heal damage, but they also damage tissues and cause degenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Adaptive immune cells can specifically target unwanted things such as viruses and tumors, but can accidentally invade healthy tissues of the body and cause autoimmune diseases such as multiple sclerosis. there is.

Colonna and colleagues-including co-lead authors Dr. Simone Brioschi (Postdoctoral Fellow), Wei-Le Wang (Postdoctoral Fellow), and Vincent Peng (Graduate Student)-have developed B cells, which are antibody-producing members. Tracked. Of the adaptive immune system. They found that most B cells in the meninges develop and mature in the bone marrow of the skull. As B cells mature, they must be taught to distinguish between normal proteins from the body that pose no threat and foreign proteins that signal infection or disease and require a response. The skull is a convenient place for this education for life-bearing B cells that orbit the boundaries of the central nervous system.

“B cells in the bone marrow of the skull come into contact with the central nervous system and are educated by the central nervous system,” said Colonna, a professor of medicine. “If they were released into the blood, that wouldn’t happen. They learn to be tolerant of proteins in the brain because they are in direct contact with the brain.”

In addition to the tolerant B cells from the skull, the researchers also found a population of B cells that enter the meninges from the blood. These blood-derived B cells are not trained to ignore normal CNS proteins. Colonna said some of these cells could mistakenly recognize harmless CNS proteins as foreign bodies and produce antibodies against them. In addition, the number of B cells from these bloods. Increases with age and provides clues as to why older people are at higher risk of neuroimmune status.

Meanwhile, Kipnis’ team is led by co-lead author Andrea Cugurra (graduate student), Tornike Mamuladze (Doctor of Medicine), visiting scholar Tornike Mamuladze (MD), and postdoctoral researcher Justin Rustenhoven (PhD). I was looking for a source of cells. A group of innate immune cells. They found that bone marrow cells originate in the bone marrow of the skull and spine and enter the meninges via direct channels through the bone.

Using a mouse model of multiple sclerosis and brain and spinal cord injury, Kipnis et al. Found that bone marrow cells clustered in the brain and spinal cord in response to injury or disease. Most of the input cells are drawn from the resident population of meningeal bone marrow cells. These are biased towards the regulation and regulation of the immune response. However, some bone marrow cells come from the blood, which are highly inflammatory and can cause damage if not properly controlled.

“Understanding where these cells come from and how they behave is an important part of understanding the basic mechanisms of neuroimmune interactions and for the neurological conditions associated with inflammation. New therapeutic approaches can be designed. ”Neurosurgery, neurology, neuroscience. “The location of these cells in the skull makes them relatively accessible and opens up the possibility of designing treatments that modify the behavior of these cells to treat neuroimmune conditions.”

reference:

Cugurra A, Mamuladze T, Rustenhoven J, and other skulls and spinal bone marrow are reservoirs of meninges and CNS parenchymal bone marrow cells. SciencePublished online on June 3, 2021. doi:10.1126 / science.abf7844

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