The brain constantly communicates with the body’s immune system. Such communication appears to be aimed at ensuring a delicate balance between defense against injury and infection and protection of healthy tissue.

Now, scientists at Washington University School of Medicine in St. Louis have revealed how the two achieve a healthy balance. The study, carried out in mice, revealed that fragments of immunostimulating proteins – called gatekeeper peptides – are produced by the brain and spinal cord of the central nervous system to maintain the brain’s immune balance and enable healthy exchange of proteins. information with the immune system.

The study, published October 30 in the journal Naturehas the potential to improve treatments for diseases such as multiple sclerosis (MS) and Alzheimer’s disease, among others.

“We discovered gatekeeper brain peptides that actively interact with the immune system to keep it in check, possibly preventing destructive immune responses,” said Jonathan Kipnis, PhD, the Alan A. and Edith L. Wolff Distinguished Professor of Pathology and Medicine. immunology and professor emeritus of pathology and immunology. BJC Investigator at WashU Medicine.

We believe that these peptides help the immune system maintain a state of “immune privilege.” We are intrigued by the possibility of developing such proteins from healthy brains into a therapy aimed at suppressing inappropriate immune responses and developing better disease-modifying therapies for neuroinflammatory diseases.

Jonathan Kipnis, PhD, Alan A. and Edith L. Wolff Distinguished Professor of Pathology and Immunology, University of Washington School of Medicine

Immune surveillance involves a subset of T cells that can mount an immune response when alerted to a threat. This alert comes in the form of a tiny protein fragment – ​​a sample of the potential threat – displayed on the surface of another group of presented immune cells. If T cells view the protein fragment as threatening, they launch an attack.

The researchers found that the gatekeeper peptides were presented by immune cells at the brain border interface, where they attracted and activated a subset of immune T cells whose function is regulatory, so that these cells attenuate responses abnormal immune systems.

Min Woo Kim, a graduate student in WashU Medicine’s Medical Scientist Training Program and a researcher in the Kipnis lab, examined the presentation of immune cells in the brain and its associated immune tissues in healthy mice. He discovered an abundance of brain proteins present in these cells, with the dominant protein being a component of the myelin sheath, the protective covering of neurons that is damaged in MS.

The researchers found that in mice with MS, these proteins were significantly reduced. By adding the missing brain-derived peptides by injecting vesicles – membrane-bound compartments – into the spinal fluid of mice with MS, scientists found that the therapy activated and expanded a subset of suppressor T cells. . Motor function improved and disease progression slowed in treated mice compared to mice given control vesicles.

“We identified a new process in the brain in which the organ actively engages with the immune system to present a healthy image of itself,” Kim said. “This picture looks different in mice with multiple sclerosis. We believe that other neuroinflammatory and even neurodegenerative diseases may have unique protein signatures presented to the immune system, opening the exciting possibility of using such signatures as a diagnostic tool for early diagnosis.”

WashU Medicine collaborators on the study include Cheryl Lichti, PhD, associate professor of pathology and immunology; Clair Crewe, PhD, assistant professor of cell biology and physiology; Maxim N. Artyomov, PhD, Alumni Endowed Professor of Pathology and Immunology; and the late Emil R. Unanue, PhD, who died before seeing the study completed. Unanue, winner of the 1995 Albert Lasker Prize for Basic Medical Research, was a pioneer in describing the interactions between T cells and presenting cells that allow the former to recognize and respond to foreign invaders.