PDGFRβ Cells Rapidly Relay Inflammatory Signal from the Circulatory System to Neurons via Chemokine CCL2

被引：166

作者：

Duan, Lihui ^{[1
,2
]}

Zhang, Xiao-Di ^{[1
,2
]}

Miao, Wan-Ying ^{[1
]}

Sun, Yun-Jun ^{[1
]}

Xiong, Guoliang ^{[1
,2
]}

Wu, Qiuzi ^{[1
]}

Li, Guangying ^{[1
]}

Yang, Ping ^{[4
]}

Yu, Hang ^{[1
,2
]}

Li, Humingzhu ^{[1
,3
]}

Wang, Yue ^{[1
,3
]}

Zhang, Min ^{[1
]}

Hu, Li-Yuan ^{[4
]}

Tong, Xiaoping ^{[5
]}

Zhou, Wen-Hao ^{[4
]}

Yu, Xiang ^{[1
,2
,3
]}

机构：

[1] Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, State Key Lab Neurosci, Inst Neurosci, Shanghai 200031, Peoples R China

[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[3] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China

[4] Fudan Univ, Childrens Hosp, Dept Neonatol, Shanghai 201102, Peoples R China

[5] Shanghai Jiao Tong Univ, Sch Med, Dept Anat & Physiol, Shanghai 200025, Peoples R China

来源：

NEURON | 2018年 / 100卷 / 01期

基金：

国家重点研发计划; 中国国家自然科学基金;

关键词：

MATERNAL IMMUNE ACTIVATION; MESSENGER-RNA EXPRESSION; CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; CYTOKINE EXPRESSION; NEUROVASCULAR UNIT; BLOOD-FLOW; PERICYTES; RECEPTOR; SINGLE;

D O I：

10.1016/j.neuron.2018.08.030

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Acute infection, if not kept in check, can lead to systemic inflammatory responses in the brain. Here, we show that within 2 hr of systemic inflammation, PDGFR beta mural cells of blood vessels rapidly secrete chemokine CCL2, which in turn increases total neuronal excitability by promoting excitatory synaptic transmission in glutamatergic neurons of multiple brain regions. By single-cell RNA sequencing, we identified Col1a1 and Rgs5 subgroups of PDGFR beta cells as the main source of CCL2. Lipopolysaccharide (LPS)- or Poly(I:C)-treated pericyte culture medium induced similar effects in a CCL2-dependent manner. Importantly, in PDGFR beta-Cre; Ccl2(fl/fl) mice, LPS-induced increase in excitatory synaptic transmission was significantly attenuated. These results demonstrate in vivo that PDGFR beta cells function as initial sensors of external insults by secreting CCL2, which relays the signal to the central nervous system. Through their gateway position in the brain, PDGFR beta cells are ideally positioned to respond rapidly to environmental changes and to coordinate responses.

引用

页码：183 / +

页数：26

共 101 条

[1] Single-cell mass cytometry reveals distinct populations of brain myeloid cells in mouse neuroinflammation and neurodegeneration models [J].