Innate immune training restores pro-reparative myeloid functions to promote remyelination in the aged central nervous system

被引：1

作者：

Tiwari, Vini ^{[1
,2
]}

Prajapati, Bharat ^{[5
]}

Asare, Yaw ^{[4
]}

Damkou, Alkmini ^{[1
,2
]}

Ji, Hao ^{[4
]}

Liu, Lu ^{[2
,4
]}

Naser, Nawraa ^{[4
]}

Gouna, Garyfallia ^{[1
,2
]}

Leszczynska, Katarzyna B. ^{[6
]}

Mieczkowski, Jakub ^{[6
,7
]}

Dichgans, Martin ^{[2
,3
,4
]}

Wang, Qing ^{[8
]}

Kawaguchi, Riki ^{[8
,11
]}

Shi, Zechuan ^{[9
]}

Swarup, Vivek ^{[9
]}

Geschwind, Daniel H. ^{[8
]}

Prinz, Marco ^{[10
,12
]}

Gokce, Ozgun ^{[3
,4
,13
,14
]}

Simons, Mikael ^{[1
,2
,3
,4
]}

机构：

[1] Tech Univ Munich, Inst Neuronal Cell Biol, D-81377 Munich, Germany

[2] German Ctr Neurodegenerat Dis DZNE, D-81377 Munich, Germany

[3] Munich Cluster Syst Neurol SyNergy, D-81377 Munich, Germany

[4] Ludwig Maximilians Univ Munchen, Univ Hosp Munich, Inst Stroke & Dementia Res, D-81377 Munich, Germany

[5] Univ Gothenburg, Inst Biomed, Sahlgrenska Acad, S-41390 Gothenburg, Sweden

[6] Polish Acad Sci, Lab Mol Neurobiol, Nencki Inst Expt Biol, Nencki Inst Expt Biol, Warsaw, Poland

[7] Med Univ Gdansk, Med Lab 3P, PL-80211 Gdansk, Poland

[8] Univ Calif Los Angeles, Dept Neurol & Human Genet, Los Angeles, CA 90095 USA

[9] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA USA

[10] Univ Freiburg, Inst Neuropathol, Fac Med, D-79085 Freiburg, Germany

[11] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, David Geffen Sch Med, Psychiat, Los Angeles, CA 90095 USA

[12] Univ Freiburg, Signalling Res Ctr BIOSS & CIBSS, D-79104 Freiburg, Germany

[13] German Ctr Neurodegenerat Dis DZNE, D-53127 Bonn, Germany

[14] Univ Hosp Bonn, Dept Neurodegenerat Dis & Geriatr Psychiat, D-53127 Bonn, Germany

来源：

IMMUNITY | 2024年 / 57卷 / 09期

基金：

欧洲研究理事会;

关键词：

CNS REMYELINATION; OLIGODENDROCYTE DIFFERENTIATION; MICROGLIA; MYELIN; BCG; MACROPHAGES; EPIGENETICS; MECHANISMS; PLATFORM; MEMORY;

D O I：

10.1016/j.immuni.2024.07.001

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：2173 / 2190.e8

页数：27

共 3 条

[1] Innate and adaptive immune mechanisms regulating central nervous system remyelination
Creswell, Richard
Dombrowski, Yvonne
CURRENT OPINION IN PHARMACOLOGY, 2022, 63
[2] Central Nervous System Remyelination: Roles of Glia and Innate Immune Cells
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Rawji, Khalil S.
Duncan, Greg J.
Ho, Madelene F. S.
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FRONTIERS IN MOLECULAR NEUROSCIENCE, 2019, 12
[3] Osteopontin (OPN)/SPP1: from its biochemistry to biological functions in the innate immune system and the central nervous system (CNS)
Lin, Elliot Yi-Hsin
Xi, Wen
Aggarwal, Nupur
Shinohara, Mari L.
INTERNATIONAL IMMUNOLOGY, 2023, 35 (04) : 171 - 180

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