Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brain

Lemaitre, P.; Tareen, S.; Pasciuto, E.; Mascali, L.; Martirosyan, A.; Callaerts-Vegh, Z.; Dooley, J.; Holt, M.; Yshii, L.; Liston, A.

doi:10.1101/2022.03.01.482519

bioRxiv · 10.1101/2022.03.01.482519

Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brain

Lemaitre, P.·Tareen, S.·Pasciuto, E.·Mascali, L.·Martirosyan, A.·Callaerts-Vegh, Z.·Dooley, J.·Holt, M.·Yshii, L.·Liston, A.

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Abstract

Cognitive decline is a common pathological outcome during aging, with an ill-defined cellular or molecular basis. Among the cellular changes observed with age are alterations to neuronal plasticity, changes in the glial compartment and the decline of the neurogenic niche. In the recent years, the concept of inflammaging, defined as a low-grade inflammation increasing with age, has emerged as a nexus for age-related diseases. This increase of basal inflammation is also observed in the central nervous system. While not classically considered a neurological cell type, infiltrating T cells increase in the brain with age, and may be responsible for amplification of inflammatory cascades and disruptions to the neurogenic niche. Recently, a small resident population of regulatory T cells has been identified in the brain, and the capacity of IL2-mediated expansion of this population to counter neuroinflammatory disease has been demonstrated. Here we test a brain-specific IL2 delivery system for the prevention of neurological decline in aging mice. We identify the molecular hallmarks of aging in the brain glial compartments, and identify partial restoration of this signature through IL2 treatment. At a behavioral level, brain IL2 delivery prevented the age-induced defect in spatial learning, without improving the general decline in motor skill or arousal. These results identify immune modulation as a potential path to preserving cognitive function for healthy ageing.

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Lemaitre, P., Tareen, S., Pasciuto, E., Mascali, L., Martirosyan, A., Callaerts-Vegh, Z., Dooley, J., Holt, M., Yshii, L., Liston, A.. 2022-03-04. Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brain. https://doi.org/10.1101/2022.03.01.482519

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