Brain actively engages with immune system to maintain health

The brain constantly engages in dialogue with the body's immune system. Such communication appears aimed at ensuring a delicate balance between defending against injury and infection and guarding healthy tissue.

Now, scientists at Washington University School of Medicine in St. Louis have revealed how the two strike a healthy balance. The study, in mice, found that fragments of immune-stimulating proteins – dubbed guardian peptides – are produced by the brain and spinal cord of the central nervous system to maintain the brain's immune balance and permit a healthy interchange of information with the immune system.

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

The researchers found that guardian peptides were presented by immune cells at the interface of the brain's borders, where they attracted and activated a subset of immune T cells whose function is regulatory, such that these cells dampen abnormal immune reactions.

Min Woo Kim, a graduate student in WashU Medicine's Medical Scientist Training Program and a researcher in the Kipnis lab, examined presenting immune cells from the brain and its associated immune tissues in healthy mice. He found an abundance of brain proteins presented by such cells, with the dominant protein being a component of myelin sheath, the protective cover on neurons that becomes damaged in MS.

WashU Medicine collaborators on the study include Cheryl Lichti, PhD, an associate professor of pathology & immunology; Clair Crewe, PhD, an assistant professor of cell biology & physiology; Maxim N. Artyomov, PhD, the Alumni Endowed Professor of Pathology & Immunology; and the late Emil R. Unanue, PhD, who died before seeing the study's completion. Unanue, a 1995 Albert Lasker Basic Medical Research Award winner, was a pioneer in describing the interactions between T cells and presenting cells that make it possible for the former to recognize and respond to foreign invaders.

Source:

Washington University School of Medicine

Journal reference:

Kim, M. W., et al. (2024). Endogenous self-peptides guard immune privilege of the central nervous system. Nature. doi.org/10.1038/s41586-024-08279-y.