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000272079 1001_ $$0P:(DE-2719)9001975$$aTiwari, Vini$$b0$$eFirst author$$udzne
000272079 245__ $$aInnate immune training restores pro-reparative myeloid functions to promote remyelination in the aged central nervous system.
000272079 260__ $$aNew York, NY$$bElsevier$$c2024
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000272079 520__ $$aThe 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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000272079 650_7 $$2Other$$aaging
000272079 650_7 $$2Other$$ainnate immunity
000272079 650_7 $$2Other$$amicroglia
000272079 650_7 $$2Other$$amyelin
000272079 650_7 $$2Other$$aremyelination
000272079 650_2 $$2MeSH$$aAnimals
000272079 650_2 $$2MeSH$$aImmunity, Innate
000272079 650_2 $$2MeSH$$aMice
000272079 650_2 $$2MeSH$$aAging: immunology
000272079 650_2 $$2MeSH$$aRemyelination
000272079 650_2 $$2MeSH$$aMicroglia: immunology
000272079 650_2 $$2MeSH$$aMicroglia: metabolism
000272079 650_2 $$2MeSH$$aMyeloid Cells: immunology
000272079 650_2 $$2MeSH$$aMyeloid Cells: metabolism
000272079 650_2 $$2MeSH$$aCentral Nervous System: immunology
000272079 650_2 $$2MeSH$$aMice, Inbred C57BL
000272079 650_2 $$2MeSH$$aMyelin Sheath: metabolism
000272079 650_2 $$2MeSH$$aMyelin Sheath: immunology
000272079 650_2 $$2MeSH$$aEpigenesis, Genetic
000272079 650_2 $$2MeSH$$aDemyelinating Diseases: immunology
000272079 650_2 $$2MeSH$$aDisease Models, Animal
000272079 7001_ $$aPrajapati, Bharat$$b1
000272079 7001_ $$aAsare, Yaw$$b2
000272079 7001_ $$0P:(DE-2719)2813094$$aDamkou, Alkmini$$b3$$udzne
000272079 7001_ $$aJi, Hao$$b4
000272079 7001_ $$0P:(DE-2719)9002890$$aLiu, Lu$$b5$$udzne
000272079 7001_ $$aNaser, Nawraa$$b6
000272079 7001_ $$0P:(DE-2719)9001859$$aGouna, Garyfallia$$b7$$udzne
000272079 7001_ $$aLeszczyńska, Katarzyna B$$b8
000272079 7001_ $$aMieczkowski, Jakub$$b9
000272079 7001_ $$0P:(DE-2719)2000030$$aDichgans, Martin$$b10$$udzne
000272079 7001_ $$0P:(DE-HGF)0$$aWang, Qing$$b11
000272079 7001_ $$aKawaguchi, Riki$$b12
000272079 7001_ $$aShi, Zechuan$$b13
000272079 7001_ $$aSwarup, Vivek$$b14
000272079 7001_ $$aGeschwind, Daniel H$$b15
000272079 7001_ $$aPrinz, Marco$$b16
000272079 7001_ $$0P:(DE-2719)9002754$$aGokce, Ozgun$$b17$$udzne
000272079 7001_ $$0P:(DE-2719)2811642$$aSimons, Mikael$$b18$$eLast author$$udzne
000272079 773__ $$0PERI:(DE-600)2001966-X$$a10.1016/j.immuni.2024.07.001$$gVol. 57, no. 9, p. 2173 - 2190.e8$$n9$$p2173 - 2190.e8$$tImmunity$$v57$$x1074-7613$$y2024
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