期刊
CELLULAR IMMUNOLOGY
卷 293, 期 1, 页码 49-58出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2014.12.005
关键词
Tim-3; Microglia; Neuron; NG2 cell; NF-kappa B; MAPK
资金
- Qianjiang Talent Program of Zhejiang Province [2012R10050]
- Zhejiang Provincial Natural Science Foundation of China [LQ13C090001]
- Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry
- Chinese Medicine Scientific Research Fund of Zhejiang Province [2012ZA086]
Microglia are the main innate immune cells in the central nervous system that are actively involved in maintaining brain homeostasis and diseases. T cell Ig and mucin domain protein 3 (Tim-3) plays critical roles in both the adaptive and the innate immune system and is an emerging therapeutic target for treatment of various disorders. In the brain Tim-3 is specifically expressed on microglia but its functional role is unclear. Here, we showed that Tim-3 was up-regulated on microglia by ATP or LPS stimulation. Tim-3 activation with antibodies increased microglia expression of TGF-beta, TNF-alpha and IL-1 beta. Blocking of Tim-3 with antibodies decreased the microglial phagocytosis of apoptotic neurons. Tim-3 blocking alleviated the detrimental effect of microglia on neurons and promoted NG2 cell differentiation in co-cultures. Finally, MAPKs namely ERK1/2 and JNK proteins were phosphorylated upon Tim-3 activation in microglia. Data indicated that Tim-3 modulates microglia activity and regulates the interaction of microglia-neural cells. (C) 2014 Elsevier Inc. All rights reserved.
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