Activating Immune Cells May Revitalize The Aging Brain

The ever important and beautiful brain is unfortunately highly susceptible to aging, as such cognitive functions such as learning and memory gradually decline as we get older. Additionally much of the body’s immune system will also deteriorate with age resulting in increased susceptibility to infection and higher levels of inflammation. 

This study reveals that aging related changes in group 2 innate lymphoid immune cells may allow physicians to combat the effects of aging on the brain; ILC2s reside in specific tissue and help with repairs when they are damaged. ILC2s in the spinal cord for instance were recently shown to promote healing after spinal cord injury. “However, whether ILC2s also reside in other parts of the central nervous system, and how they respond to aging, was unknown,” Qi Yang says. 

Brains of old and young mice were examined, ILC2s were found to accumulate with age in the choroid plexus structure which produces cerebrospinal fluid and is close to the hippocampus; older mouse brains had as much as 5 times as many ILC2 cells as younger brains, and the researchers also saw large numbers of ILC2s in the choroid plexus of elderly humans. 

ILC2s were largely inactive or in a quiescent state in the older mouse brains, they were activated by treating the mice with IL-33 cell signalling molecules, which caused the cells to proliferate and produce proteins that stimulate the formation and survival of neurons. Upon activation ILC2s from the older mice were able to live longer and produce more ILC2 when compared with ILC2s from younger animals, according to the researchers. 

Injecting or treating old mice with IL-33 cells pre-activated in the lab was observed to improve the animal’s performance in a series of cognitive tests that were designed to measure their learning and memory.  “This suggested that activated ILC2 can improve the cognitive function of aged mice,” says Kristen L. Zuloaga.

One of the proteins produced by the activated ILC2s is called the IL-5 signalling molecule and treating old mice with IL-5 was found to increase formation of new nerve cells in the hippocampus and reduce the amount of potentially damaging inflammation in the brain, as well as improve cognitive performance of aged mice in a number of tests in this study. 

“Our work has thus revealed the accumulation of tissue-resident ILC2 cells in the choroid plexus of aged brains and demonstrated that their activation may revitalize the aged brain and alleviate aging-associated cognitive decline,” says Yang.

“Aging is the major risk factor for a variety of neurocognitive and neurodegenerative diseases,” says Zuloaga. “Targeting ILC2 cells in the aged brain may provide new avenues to combat these diseases in humans.”