Blocking A(2B) Adenosine Receptor Alleviates Pathogenesis of Experimental Autoimmune Encephalomyelitis via Inhibition of IL-6 Production and Th17 Differentiation

doi:10.4049/jimmunol.1103721

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	Blocking A(2B) Adenosine Receptor Alleviates Pathogenesis of Experimental Autoimmune Encephalomyelitis via Inhibition of IL-6 Production and Th17 Differentiation
	Wei, Wei 2,3; Du, Changsheng 3; Lv, Jie 2,3; Zhao, Guixian 4,5; Li, Zhenxin 4,5; Wu, Zhiying 4,5; Hasko, Gyoergy 1; Xie, Xin2,3
刊名	JOURNAL OF IMMUNOLOGY
	2013
卷号	190 期号:1 页码:138-146
ISSN号	0022-1767
DOI	10.4049/jimmunol.1103721
文献子类	Article
英文摘要	Adenosine is a key endogenous signaling molecule that regulates immune responses. A(2B) adenosine receptor (AR) is a relatively low-affinity receptor for adenosine, and the activation of A(2B)AR is believed to require pathological level of adenosine that is associated with ischemia, inflammation, trauma, or other types of stress. The role of A(2B)AR in the pathogenesis of multiple sclerosis (MS) is still unclear. In this study, we discovered that A(2B)AR was upregulated both in the peripheral blood leukocytes of MS patients and the peripheral lymphoid tissues of experimental autoimmune encephalomyelitis (EAE) mice. A(2B)AR-specific antagonists, CVT-6883 and MRS-1754, alleviated the clinical symptoms of EAE and protected the CNS from immune damage. A(2B)AR-knockout mice also developed less severe EAE. Further study indicated that blocking or deleting A(2B)AR inhibited Th17 cell differentiation by blocking IL-6 production from APCs such as dendritic cells. In dendritic cells, A(2B)AR was also upregulated during the development of EAE. CVT-6883 and genetic deletion of A(2B)AR significantly reduced adenosine-mediated IL-6 production. The phospholipase C beta-protein kinase C and p38 MAPK pathways were found to be involved in the A(2B)AR-mediated IL-6 production. Our findings not only revealed the pathological role of A(2B)AR in EAE, but also suggested that this receptor might be a new therapeutic target for the development of anti-MS drugs. The Journal of Immunology, 2013, 190: 138-146.
资助项目	National Natural Science Foundation of China[31000399] ; National Natural Science Foundation of China[31171348] ; National Natural Science Foundation of China[81202341] ; Ministry of Science and Technology of China[2012CB910404] ; Ministry of Science and Technology of China[2009CB940900] ; Chinese Academy of Sciences[XDA01040301] ; Shanghai Commission of Science and Technology[12XD1402100]
WOS关键词	CENTRAL-NERVOUS-SYSTEM ; HUMAN DENDRITIC CELLS ; ACUTE LUNG INJURY ; MULTIPLE-SCLEROSIS ; HUMAN-LYMPHOCYTES ; UP-REGULATION ; EXPRESSION ; ACTIVATION ; COLITIS ; CD73
WOS研究方向	Immunology
语种	英语
出版者	AMER ASSOC IMMUNOLOGISTS
WOS记录号	WOS:000312832500016
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277829]
专题	国家新药筛选中心
通讯作者	Xie, Xin
作者单位	1.Univ Med & Dent New Jersey, Dept Surg, Newark, NJ 07103 USA 2.Chinese Acad Sci, CAS Key Lab Receptor Res, Natl Ctr Drug Screening, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 3.Tongji Univ, Lab Receptor Based Biomed, Shanghai Key Lab Signaling & Dis Res, Sch Life Sci & Technol, Shanghai 200092, Peoples R China; 4.Fudan Univ, Huashan Hosp, Dept Neurol, Shanghai 200040, Peoples R China; 5.Fudan Univ, Inst Neurol, Shanghai 200040, Peoples R China;
推荐引用方式 GB/T 7714	Wei, Wei,Du, Changsheng,Lv, Jie,et al. Blocking A(2B) Adenosine Receptor Alleviates Pathogenesis of Experimental Autoimmune Encephalomyelitis via Inhibition of IL-6 Production and Th17 Differentiation[J]. JOURNAL OF IMMUNOLOGY,2013,190(1):138-146.
APA	Wei, Wei.,Du, Changsheng.,Lv, Jie.,Zhao, Guixian.,Li, Zhenxin.,...&Xie, Xin.(2013).Blocking A(2B) Adenosine Receptor Alleviates Pathogenesis of Experimental Autoimmune Encephalomyelitis via Inhibition of IL-6 Production and Th17 Differentiation.JOURNAL OF IMMUNOLOGY,190(1),138-146.
MLA	Wei, Wei,et al."Blocking A(2B) Adenosine Receptor Alleviates Pathogenesis of Experimental Autoimmune Encephalomyelitis via Inhibition of IL-6 Production and Th17 Differentiation".JOURNAL OF IMMUNOLOGY 190.1(2013):138-146.