CSF-1 controls cerebellar microglia and is required for motor function and social interaction

被引：140

作者：

Kana, Veronika ^{[1
,2
,3
]}

Desland, Fiona A. ^{[1
,2
,3
]}

Casanova-Acebes, Maria ^{[1
,2
,3
]}

Ayata, Pinar ^{[4
,5
,6
]}

Badimon, Ana ^{[4
,5
,6
]}

Nabel, Elisa ^{[4
,5
,7
,8
,9
]}

Yamamuro, Kazuhiko ^{[4
,5
,7
,8
,9
]}

Sneeboer, Marjolein ^{[10
,11
]}

Tan, I-Li ^{[12
]}

Flanigan, Meghan E. ^{[4
,5
]}

Rose, Samuel A. ^{[13
]}

Chang, Christie ^{[1
,2
,3
]}

Leader, Andrew ^{[1
,2
,3
]}

Le Bourhis, Hortense ^{[1
,2
,3
]}

Sweet, Eric S. ^{[4
,5
]}

Tung, Navpreet ^{[1
,2
,3
]}

Wroblewska, Aleksandra ^{[13
]}

Lavin, Yonit ^{[1
,2
,3
]}

See, Peter ^{[14
]}

Baccarini, Alessia ^{[13
]}

Ginhoux, Florent ^{[14
]}

Chitu, Violeta ^{[15
]}

Stanley, E. Richard ^{[15
]}

Russo, Scott J. ^{[4
,5
]}

Yue, Zhenyu ^{[4
,5
]}

Brown, Brian D. ^{[13
]}

Joyner, Alexandra L. ^{[12
]}

De Witte, Lotje D. ^{[7
,10
,11
]}

Morishita, Hirofumi ^{[4
,5
,7
,8
,9
]}

Schaefer, Anne ^{[4
,5
,6
]}

Merad, Miriam ^{[1
,2
,3
]}

机构：

[1] Icahn Sch Med Mt Sinai, Dept Oncol Sci, New York, NY 10029 USA

[2] Icahn Sch Med Mt Sinai, Precis Immunol Inst, New York, NY 10029 USA

[3] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA

[4] Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA

[5] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA

[6] Icahn Sch Med Mt Sinai, Ronald M Loeb Ctr Alzheimers Dis, New York, NY 10029 USA

[7] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA

[8] Icahn Sch Med Mt Sinai, Dept Ophthalmol, New York, NY USA

[9] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA

[10] Univ Utrecht, Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, Utrecht, Netherlands

[11] Univ Utrecht, Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Translat Neurosci, Utrecht, Netherlands

[12] Mem Sloan Kettering Canc Ctr, Dev Biol Program, 1275 York Ave, New York, NY 10021 USA

[13] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA

[14] Agcy Sci Technol & Res, Singapore Immunol Network, Singapore, Singapore

[15] Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10467 USA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2019年 / 216卷 / 10期

基金：

美国国家卫生研究院; 新加坡国家研究基金会;

关键词：

TRANSLATIONAL PROFILING APPROACH; COLONY-STIMULATING FACTOR; DENDRITIC SPINES; LANGERHANS CELLS; BRAIN; MACROPHAGE; EXPRESSION; MOUSE; FATE; OSTEOPETROSIS;

D O I：

10.1084/jem.20182037

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Microglia, the brain resident macrophages, critically shape forebrain neuronal circuits. However, their precise function in the cerebellum is unknown. Here we show that human and mouse cerebellar microglia express a unique molecular program distinct from forebrain microglia. Cerebellar microglial identity was driven by the CSF-1R ligand CSF-1, independently of the alternate CSF-1R ligand, IL-34. Accordingly, CSF-1 depletion from Nestin. cells led to severe depletion and transcriptional alterations of cerebellar microglia, while microglia in the forebrain remained intact. Strikingly, CSF-1 deficiency and alteration of cerebellar microglia were associated with reduced Purkinje cells, altered neuronal function, and defects in motor learning and social novelty interactions. These findings reveal a novel CSF-1-CSF-1R signaling-mediated mechanism that contributes to motor function and social behavior.

引用

页码：2265 / 2281

页数：17

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