Home > Publications Database > Innate immune training restores pro-reparative myeloid functions to promote remyelination in the aged central nervous system. > print

001     272079
005     20240929004836.0
024 7 _ |a 10.1016/j.immuni.2024.07.001
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024 7 _ |a 1074-7613
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024 7 _ |a 1097-4180
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037 _ _ |a DZNE-2024-01122
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Tiwari, Vini
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245 _ _ |a Innate immune training restores pro-reparative myeloid functions to promote remyelination in the aged central nervous system.
260 _ _ |a New York, NY
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520 _ _ |a The reduced ability of the central nervous system to regenerate with increasing age limits functional recovery following demyelinating injury. Previous work has shown that myelin debris can overwhelm the metabolic capacity of microglia, thereby impeding tissue regeneration in aging, but the underlying mechanisms are unknown. In a model of demyelination, we found that a substantial number of genes that were not effectively activated in aged myeloid cells displayed epigenetic modifications associated with restricted chromatin accessibility. Ablation of two class I histone deacetylases in microglia was sufficient to restore the capacity of aged mice to remyelinate lesioned tissue. We used Bacillus Calmette-Guerin (BCG), a live-attenuated vaccine, to train the innate immune system and detected epigenetic reprogramming of brain-resident myeloid cells and functional restoration of myelin debris clearance and lesion recovery. Our results provide insight into aging-associated decline in myeloid function and how this decay can be prevented by innate immune reprogramming.
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650 _ 7 |a aging
|2 Other
650 _ 7 |a innate immunity
|2 Other
650 _ 7 |a microglia
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650 _ 7 |a myelin
|2 Other
650 _ 7 |a remyelination
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650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Immunity, Innate
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Aging: immunology
|2 MeSH
650 _ 2 |a Remyelination
|2 MeSH
650 _ 2 |a Microglia: immunology
|2 MeSH
650 _ 2 |a Microglia: metabolism
|2 MeSH
650 _ 2 |a Myeloid Cells: immunology
|2 MeSH
650 _ 2 |a Myeloid Cells: metabolism
|2 MeSH
650 _ 2 |a Central Nervous System: immunology
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650 _ 2 |a Mice, Inbred C57BL
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650 _ 2 |a Myelin Sheath: metabolism
|2 MeSH
650 _ 2 |a Myelin Sheath: immunology
|2 MeSH
650 _ 2 |a Epigenesis, Genetic
|2 MeSH
650 _ 2 |a Demyelinating Diseases: immunology
|2 MeSH
650 _ 2 |a Disease Models, Animal
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700 1 _ |a Prajapati, Bharat
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700 1 _ |a Asare, Yaw
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700 1 _ |a Damkou, Alkmini
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700 1 _ |a Ji, Hao
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700 1 _ |a Liu, Lu
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700 1 _ |a Naser, Nawraa
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700 1 _ |a Gouna, Garyfallia
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700 1 _ |a Leszczyńska, Katarzyna B
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700 1 _ |a Mieczkowski, Jakub
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700 1 _ |a Dichgans, Martin
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700 1 _ |a Wang, Qing
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700 1 _ |a Kawaguchi, Riki
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700 1 _ |a Shi, Zechuan
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700 1 _ |a Swarup, Vivek
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700 1 _ |a Geschwind, Daniel H
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700 1 _ |a Prinz, Marco
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700 1 _ |a Gokce, Ozgun
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700 1 _ |a Simons, Mikael
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773 _ _ |a 10.1016/j.immuni.2024.07.001
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