Astrocyte-derived interleukin-33 promotes microglial synapse engulfment and neural circuit development

被引：562

作者：

Vainchtein, Ilia D. ^{[1
]}

Chin, Gregory ^{[1
]}

Cho, Frances S. ^{[5
,7
]}

Kelley, Kevin W. ^{[1
]}

Miller, John G. ^{[1
]}

Chien, Elliott C. ^{[1
]}

Liddelow, Shane A. ^{[8
,11
,12
]}

Nguyen, Phi T. ^{[1
,6
]}

Nakao-Inoue, Hiromi ^{[1
]}

Dorman, Leah C. ^{[1
,5
]}

Akil, Omar ^{[3
]}

Joshita, Satoru ^{[9
,10
]}

Barres, Ben A. ^{[8
]}

Paz, Jeanne T. ^{[4
,7
]}

Molofsky, Ari B. ^{[2
]}

Molofsky, Anna V. ^{[1
]}

机构：

[1] Univ Calif San Francisco, Dept Psychiat, Weill Inst Neurosci, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Dept Otolaryngol, San Francisco, CA 94143 USA

[4] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA

[5] Univ Calif San Francisco, Neurosci Grad Program, San Francisco, CA 94143 USA

[6] Univ Calif San Francisco, Biomed Sci Grad Program, San Francisco, CA 94143 USA

[7] Gladstone Inst Neurol Dis, San Francisco, CA 94158 USA

[8] Stanford Univ, Dept Neurobiol, Palo Alto, CA 94304 USA

[9] Shinshu Univ, Div Gastroenterol & Hepatol, Dept Med, Sch Med, Matsumoto, Nagano, Japan

[10] Shinshu Univ, Res Ctr Next Generat Med, Matsumoto, Nagano, Japan

[11] NYU, Neurosci Inst, Langone Med Sch, New York, NY USA

[12] NYU, Dept Neurosci & Physiol, Langone Med Sch, New York, NY USA

来源：

SCIENCE | 2018年 / 359卷 / 6381期

基金：

美国国家科学基金会; 英国医学研究理事会;

关键词：

INJURY; BRAIN; HOMEOSTASIS; ROLES; CNS; INFLAMMATION; RECOVERY; IL-33; GLIA;

D O I：

10.1126/science.aal3589

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Neuronal synapse formation and remodeling are essential to central nervous system (CNS) development and are dysfunctional in neurodevelopmental diseases. Innate immune signals regulate tissue remodeling in the periphery, but how this affects CNS synapses is largely unknown. Here, we show that the interleukin-1 family cytokine interleukin-33 (IL-33) is produced by developing astrocytes and is developmentally required for normal synapse numbers and neural circuit function in the spinal cord and thalamus. We find that IL-33 signals primarily to microglia under physiologic conditions, that it promotes microglial synapse engulfment, and that it can drive microglial-dependent synapse depletion in vivo. These data reveal a cytokine-mediated mechanism required to maintain synapse homeostasis during CNS development.

引用

页码：1269 / 1273

页数：5

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