Immune cells identified as therapeutic target for age-related cognitive decline in mice

Written by Alice Bough (Future Science Group)

A team of scientists from Albany Medical College (NY, USA) has identified that group 2 innate lymphoid cells (ILC2s) accumulate in aging brains. They determined that activation of these cells may prevent cognitive decline.

The paper, published in the Journal of Experimental Medicine, suggests that these cells could be a new target for the treatment of age-related neurodegenerative diseases.

Previous research has determined that ILC2s can reside in the meninges where they can play a role in tissue repair following spinal cord injury. “However, whether ILC2s also reside in other parts of the central nervous system, and how they respond to aging, was unknown,” explained Qi Yang (Albany Medical College).

To investigate the role of these immune cells in other brain barrier structures, the brains of young and old mice were compared. It was identified that up to five-times as many ILC2s were present in the choroid plexuses of the old mice.

It was also observed that ILC2s were found in high numbers in the choroid plexuses of humans over the age of 65.

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To assess the impact of ILC2 activation on cognition and learning, old mice were injected with pre-activated ILC2s and undertook a series of behavioral tests. Mice that had received the activated cells performed better than those which had not.

“This suggested that activated ILC2 can improve the cognitive function of aged mice,” commented Kristen Zuloaga (Albany Medical College).

The researchers identified that the mechanism by which the immune cells acted against cognitive decline involved IL-5. It was determined that this signaling molecule promoted the formation of new nerve cells in the hippocampus and also reduced brain inflammation.

“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,” stated Yang.

Looking forward, the group hope that their findings can be translated into human medicine. “Aging is the major risk factor for a variety of neurocognitive and neurodegenerative diseases,” concluded Zuloaga. “Targeting ILC2 cells in the aged brain may provide new avenues to combat these diseases in humans.”

Sources: Fung ITH, Sankar P, Zhang Y et al. Activation of group 2 innate lymphoid cells alleviates aging-associated cognitive decline. J. Exp. Med. 217(4), e20190915 (2020); EurekAlert. Activating immune cells could revitalize the aging brain, study suggests. Press release: www.eurekalert.org/