Cell paper interpretation! Reveal new mechanisms by which the immune system monitors the brain

February 4, 2021 /--- Alzheimer's Disease, Multiple Sclerosis, Autism, Schizophrenia, and many other neurological and psychiatric disorders are all associated with inflammation in the brain.
evidence that immune cells and molecules also play a key role in the normal development and function of the brain.
but at the heart of the emerging field of neuroimmunes is a mystery: How does the immune system know what's going on in the brain? Generations of students have been told that the brain is immune, meaning that the immune system largely avoids the brain.
, in a new study, researchers from the St. Louis School of Medicine at Washington University in the United States believe they have figured out how the immune system monitors what happens in the brain.
immune cells are stationed in meninges ---the tissue that covers the brain and spinal cord--- and are sampled there when the fluid is flushed out of the brain.
if the cells detect signs of infection, disease or injury, they are prepared to initiate an immune response to the problem, the researchers said.
the findings open up the possibility of targeting immune cells located in such surveillance sites as a means of treating diseases driven by inflammation in the brain.
results were published online January 27, 2021 in the journal Cell under the title "Functionalization of the dural sinuses as a neuroimmune interface."
from Cell, 2021, doi:10.1016/j.cell.2020.12.040.
s organs are monitored by the immune system," said Dr. Jonathan Kipnis, a professor of pathology and immunology at The University of Washington's St. Louis School of Medicine and author of the paper.
if there are tumors, injuries and infections anywhere in the body, the immune system must know this.
but people say the brain is the exception; if you have a problem with the brain, the immune system lets it happen.
doesn't make sense to me.
we found that there is an immune surveillance of the brain--- only outside the brain.
now we know where it happened, which offers many new possibilities for regulating the immune system.
2015, Kipnis and his colleagues discovered a network of blood vessels that drain fluid and small molecules from the brain into the lymph nodes, where the immune response starts.
the findings prove a direct physical link between the brain and the immune system.
but this network of blood vessels represents an outlet for the brain.
still unclear where immune cells enter or monitor the brain.
Kipnis and the paper's first author, postdoctoral researcher Justin Rustenhoven, began looking for the immune system to enter the brain.
they found a clue that the blood vessels containing the fluid leaving the brain were parallel to the sinuses in the epidural, the hard outer layer beneath the skull.
meninges contain blood that carries immune cells, and lacks the tight barriers that separate blood from the brain elsewhere.
have shown that the epidural sinuses are filled with molecules from the brain and immune cells carried in the blood.
immune cells, some of which can be obtained from the blood and display suspicious molecules, while others can scan for suspicious molecules and defend them against them.
, "Imagine if your neighbor looked through your trash every day," says Kipnis, a neighbor.
if they start finding blood-stained towels in your trash can, they know there's a problem.
is true of the immune system.
if the immune cells on patrol see signs of tumor antigens or infections from the brain, they know there's a problem.
they take the evidence to the immune headquarters, the lymph nodes, and initiate an immune response.
the results show that the immune system sees the brain from a distance and only enters when problems are detected.
may explain why the brain has long been considered immune.
, "Immune activity in the brain can be very harmful, " says Rustenhoven.
it can kill neurons and cause swelling.
the brain can't tolerate too much swelling because the skull is a fixed volume.
so immune surveillance is pushed to the boundary, where cells can still monitor the brain, but there is no risk of damage to the brain.
" multiple sclerosis is a degenerative disease in which the immune system attacks the protective crucible on the nerves, causing communication problems between the brain and other parts of the body.
reason for this is not clear.
The researchers used mouse models of multiple sclerosis to find that the initiation of the disease triggered a massive build-up of activated immune cells in the meninges, suggesting that harmful immune responses may start with the epidural and spread to the brain.
the role of epidural sinuses in neuro-inflammatory diseases requires further research to verify.
, however, the position of the epidural sinuses is only on the inside of the skull where the blood-brain barrier is accessed, suggesting that it is possible to target the immune system in this area.
if this is a gateway to the brain, we can try to manipulate this area with therapy designed to prevent overactive immune cells from entering the brain," Kipnis said.
the epidural is so close to the surface that we can even deliver the drug through the skull.
theory, you can come up with an ointment that spreads through the skull to the epidural.
we may have found where the inflammatory response to many neuroimmune conditions starts, and there are many things we can do about it.
" (Bioon.com) Reference: 1. Justin Rustenhoven et al. Functional characterization of the dural sinuses as a neuroimmune interface. Cell, 2021, doi:10.1016/j.cell.2020.12.040.2.How does the immune system keep tabs on the brain?