Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brain
Abstract Cognitive decline is a common pathological outcome during aging, with an ill‐defined molecular and cellular basis. In recent years, the concept of inflammaging, defined as a low‐grade inflammation increasing with age, has emerged. Infiltrating T cells accumulate in the brain with age and ma...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2023-05-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202216805 |
| _version_ | 1797279754418651136 |
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| author | Pierre Lemaitre Samar HK Tareen Emanuela Pasciuto Loriana Mascali Araks Martirosyan Zsuzsanna Callaerts‐Vegh Suresh Poovathingal James Dooley Matthew G Holt Lidia Yshii Adrian Liston |
| author_facet | Pierre Lemaitre Samar HK Tareen Emanuela Pasciuto Loriana Mascali Araks Martirosyan Zsuzsanna Callaerts‐Vegh Suresh Poovathingal James Dooley Matthew G Holt Lidia Yshii Adrian Liston |
| author_sort | Pierre Lemaitre |
| collection | DOAJ |
| description | Abstract Cognitive decline is a common pathological outcome during aging, with an ill‐defined molecular and cellular basis. In recent years, the concept of inflammaging, defined as a low‐grade inflammation increasing with age, has emerged. Infiltrating T cells accumulate in the brain with age and may contribute to the amplification of inflammatory cascades and disruptions to the neurogenic niche observed with age. 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 aging. |
| first_indexed | 2024-03-07T16:30:33Z |
| format | Article |
| id | doaj.art-78934a3a099a43c781c47882cc383255 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T16:30:33Z |
| publishDate | 2023-05-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-78934a3a099a43c781c47882cc3832552024-03-03T10:44:15ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842023-05-01155n/an/a10.15252/emmm.202216805Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brainPierre Lemaitre0Samar HK Tareen1Emanuela Pasciuto2Loriana Mascali3Araks Martirosyan4Zsuzsanna Callaerts‐Vegh5Suresh Poovathingal6James Dooley7Matthew G Holt8Lidia Yshii9Adrian Liston10VIB Center for Brain and Disease Research Leuven BelgiumImmunology Programme The Babraham Institute Babraham UKVIB Center for Brain and Disease Research Leuven BelgiumVIB Center for Brain and Disease Research Leuven BelgiumVIB Center for Brain and Disease Research Leuven BelgiumLaboratory of Biological Psychology, Faculty of Psychology KU Leuven Leuven BelgiumVIB Center for Brain and Disease Research Leuven BelgiumImmunology Programme The Babraham Institute Babraham UKVIB Center for Brain and Disease Research Leuven BelgiumVIB Center for Brain and Disease Research Leuven BelgiumVIB Center for Brain and Disease Research Leuven BelgiumAbstract Cognitive decline is a common pathological outcome during aging, with an ill‐defined molecular and cellular basis. In recent years, the concept of inflammaging, defined as a low‐grade inflammation increasing with age, has emerged. Infiltrating T cells accumulate in the brain with age and may contribute to the amplification of inflammatory cascades and disruptions to the neurogenic niche observed with age. 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 aging.https://doi.org/10.15252/emmm.202216805AgingBrainGene TherapyInterleukin 2Regulatory T cells |
| spellingShingle | Pierre Lemaitre Samar HK Tareen Emanuela Pasciuto Loriana Mascali Araks Martirosyan Zsuzsanna Callaerts‐Vegh Suresh Poovathingal James Dooley Matthew G Holt Lidia Yshii Adrian Liston Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brain EMBO Molecular Medicine Aging Brain Gene Therapy Interleukin 2 Regulatory T cells |
| title | Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brain |
| title_full | Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brain |
| title_fullStr | Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brain |
| title_full_unstemmed | Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brain |
| title_short | Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brain |
| title_sort | molecular and cognitive signatures of ageing partially restored through synthetic delivery of il2 to the brain |
| topic | Aging Brain Gene Therapy Interleukin 2 Regulatory T cells |
| url | https://doi.org/10.15252/emmm.202216805 |
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