Journal Article

DZNE-2024-01122

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Innate immune training restores pro-reparative myeloid functions to promote remyelination in the aged central nervous system.

Tiwari, V. (First author)DZNE* ; Prajapati, B. ; Asare, Y. ; Damkou, A.DZNE* ; Ji, H. ; Liu, L.DZNE* ; Naser, N. ; Gouna, G.DZNE* ; Leszczyńska, K. B. ; Mieczkowski, J. ; Dichgans, M.DZNE* ; Wang, Q. ; Kawaguchi, R. ; Shi, Z. ; Swarup, V. ; Geschwind, D. H. ; Prinz, M. ; Gokce, O.DZNE* ; Simons, M. (Last author)DZNE*

2024
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.immuni.2024.07.001

Abstract: 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.

Keyword(s): Animals (MeSH) ; Immunity, Innate (MeSH) ; Mice (MeSH) ; Aging: immunology (MeSH) ; Remyelination (MeSH) ; Microglia: immunology (MeSH) ; Microglia: metabolism (MeSH) ; Myeloid Cells: immunology (MeSH) ; Myeloid Cells: metabolism (MeSH) ; Central Nervous System: immunology (MeSH) ; Mice, Inbred C57BL (MeSH) ; Myelin Sheath: metabolism (MeSH) ; Myelin Sheath: immunology (MeSH) ; Epigenesis, Genetic (MeSH) ; Demyelinating Diseases: immunology (MeSH) ; Disease Models, Animal (MeSH) ; aging ; innate immunity ; microglia ; myelin ; remyelination

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Contributing Institute(s):

1. Molecular Neurobiology (AG Simons)
2. Clinical Research (Munich) (Clinical Research (Munich))
3. Spatial Dynamics of Neurodegeneration (AG Gokce)
4. Vascular Cognitive Impairment & Post-Stroke Dementia (AG Dichgans)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)
2. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2024

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 30 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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