Brain actively engages with immune system to maintain health

The brain is in constant dialogue with the body’s immune system. Such communication appears aimed at ensuring a delicate balance between defending against injury and infection and monitoring healthy tissue.

Now scientists from Washington University School of Medicine in St. Louis have revealed how the two achieve a healthy balance. The study in mice showed that fragments of immune-stimulating proteins – so-called Guardian 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 information with the immune system. to make.

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

“We found peptides in the brain that actively work with the immune system to keep it in check, preventing potentially destructive immune responses,” said Jonathan Kipnis, PhD, the Alan A. and Edith L. Wolff Distinguished Professor of Pathology & Immunology and a BJC researcher at WashU Medicine.

We think that such 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 to suppress inappropriate immune responses and develop better disease-modifying therapies for neuroinflammatory diseases.”

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

Immune surveillance involves a subset of T cells that can initiate an immune response when alerted to a threat. That warning comes in the form of a small protein fragment – ​​an example of the potential threat – that appears on the surface of another group of presenting immune cells. If T cells perceive the protein fragment as threatening, they mount an attack.

The researchers found that protective 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 dampen abnormal immune responses.

Min Woo Kim, a graduate student in WashU Medicine’s Medical Scientist Training Program and researcher in the Kipnis lab, examined the presence of brain immune cells and associated immune tissues in healthy mice. He discovered a plethora of brain proteins presented by such cells, with the dominant protein being part of the myelin sheath, the protective layer on neurons that becomes damaged in MS.

The researchers found that such proteins were drastically depleted in mice with MS. By adding the missing brain-derived peptides via injection of vesicles – membrane-bound compartments – into the cerebrospinal fluid of mice with MS, the scientists found that the therapy activated and expanded a subset of suppressor T cells. Motor function improved and disease progression slowed in the treated mice compared to mice given control blisters.

“We have identified a new process in the brain where the organ actively works with the immune system to present a healthy image of itself,” Kim said. “That picture looks different in mice with multiple sclerosis. We think that other neuroinflammatory and even neurodegenerative diseases may have unique protein signatures that are presented to the immune system, which opens up 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, the Alumni Endowed Professor of Pathology and Immunology; and the late Emil R. Unanue, PhD, who died before seeing the study’s completion. Unanue, winner of the Albert Lasker Basic Medical Research Award in 1995, was a pioneer in describing the interactions between T cells and presenting cells that allow the former to recognize and respond to foreign invaders.