PD-1 and PD-L1 mediated immune checkpoint in synapse elimination by glia = 신경 교세포에 의한 시냅스 제거과정 중 PD-1과 PD-L1의 포식 작용 억제 기전 연구

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Glial cells in the brain regulate synaptic pruning by phagocytosing redundant synapses in the healthy brain; however, the mechanisms that signal to the glial cells to avoid engulfing necessary synapses remain unknown. In this study, we demonstrate that immune system’s “don’ eat me signal”, PD-1 and PD-L1, also protects synapses from being engulfed by glia. We found that PD-1 expression peaks in the hippocampus during early developmental period and that receptor expression is localized in astrocytes and microglia. The ligand, PD-L1, was found to be expressed on the synapses of neurons, specifically on both excitatory and inhibitory pre-synapses and excitatory post-synapses. PD-1 deficient mice exhibited increased PD-L1 expressions on pre-synapses, which were not correlated with the activation of astrocytes. In addition, in vitro engulfment assay showed PD-1-PD-L1 binding can reduce phagocytosis of synaptosome-pHrodo by astrocytes. Taken together, these results demonstrate PD-1-PD-L1 signaling inhibits astrocyte phagocytosis and that the molecular brakes of glia-mediated synapse elimination can be crucial for appropriate brain development.
Advisors
Chung, Wonsukresearcher정원석researcher
Description
한국과학기술원 :생명과학과,
Publisher
한국과학기술원
Issue Date
2019
Identifier
325007
Language
eng
Description

학위논문(석사) - 한국과학기술원 : 생명과학과, 2019.2,[ii, 24 p. :]

Keywords

Don't eat me signal▼aastrocyte▼asynapse elimination▼aphagocytosis; 면역억제▼a신경교세포▼a시냅스 가지치기▼a식균 작용

URI
http://hdl.handle.net/10203/266281
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=843200&flag=dissertation
Appears in Collection
BS-Theses_Master(석사논문)
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