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学科主题: 公共卫生
题名:
Dihydroartemisinin Ameliorates Inflammatory Disease by Its Reciprocal Effects on Th and Regulatory T Cell Function via Modulating the Mammalian Target of Rapamycin Pathway
作者: Zhao, Yan G.1,2,3; Wang, Yunqi1,2; Guo, Zengli1,2; Gu, Ai-di1,2; Dan, Han C.1,4; Baldwin, Albert S.1,4; Hao, Weidong3; Wan, Yisong Y.1,2
刊名: JOURNAL OF IMMUNOLOGY
发表日期: 2012-11-01
DOI: 10.4049/jimmunol.1200919
卷: 189, 期:9, 页:4417-4425
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Immunology
研究领域[WOS]: Immunology
关键词[WOS]: AUTOIMMUNE ENCEPHALOMYELITIS ; AKT-MTOR ; ARTEMISININ ; LINEAGE ; DIFFERENTIATION ; SUPPRESSION ; MECHANISMS ; GENERATION ; T(H)17 ; GAMMA
英文摘要:

Dihydroartemisinin (DHA) is an important derivative of the herb medicine Artemisia annua L., used in ancient China. DHA is currently used worldwide to treat malaria by killing malaria-causing parasites. In addition to this prominent effect, DHA is thought to regulate cellular functions, such as angiogenesis, tumor cell growth, and immunity. Nonetheless, how DHA affects T cell function remains poorly understood. We found that DHA potently suppressed Th cell differentiation in vitro. Unexpectedly, however, DHA greatly promoted regulatory T cell (Treg) generation in a manner dependent on the TGF-beta R: Smad signal. In addition, DHA treatment effectively reduced onset of experimental autoimmune encephalomyelitis (EAE) and ameliorated ongoing EAE in mice. Administration of DHA significantly decreased Th but increased Tregs in EAE-inflicted mice, without apparent global immune suppression. Moreover, DHA modulated the mammalian target of rapamycin (mTOR) pathway, because mTOR signal was attenuated in T cells upon DHA treatment. Importantly, enhanced Akt activity neutralized DHA-mediated effects on T cells in an mTOR-dependent fashion. This study therefore reveals a novel immune regulatory function of DHA in reciprocally regulating Th and Treg cell generation through the modulating mTOR pathway. It addresses how DHA regulates immune function and suggests a new type of drug for treating diseases in which mTOR activity is to be tempered. The Journal of Immunology, 2012, 189: 4417-4425.

语种: 英语
项目资助者: China Scholarship Council ; National Institutes of Health/National Institute of Allergy and Infectious Diseases ; Lupus Research Institute, and the University Cancer Research Fund
WOS记录号: WOS:000310200600028
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51441
Appears in Collections:北京大学公共卫生学院_毒理学系_期刊论文

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作者单位: 1.Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
2.Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA
3.Peking Univ, Dept Toxicol, Sch Publ Hlth, Beijing 100191, Peoples R China
4.Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA

Recommended Citation:
Zhao, Yan G.,Wang, Yunqi,Guo, Zengli,et al. Dihydroartemisinin Ameliorates Inflammatory Disease by Its Reciprocal Effects on Th and Regulatory T Cell Function via Modulating the Mammalian Target of Rapamycin Pathway[J]. JOURNAL OF IMMUNOLOGY,2012,189(9):4417-4425.
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