Artemisinin analogue SM934 attenuate collagen-induced arthritis by suppressing T follicular helper cells and T helper 17 cells

doi:10.1038/srep38115

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	Artemisinin analogue SM934 attenuate collagen-induced arthritis by suppressing T follicular helper cells and T helper 17 cells
	Lin, Ze-Min 1,2; Yang, Xiao-Qian 2; Zhu, Feng-Hua 2; He, Shi-Jun2 ; Tang, Wei2 ; Zuo, Jian-Ping1,2
刊名	SCIENTIFIC REPORTS
	2016-11-29
卷号	6
ISSN号	2045-2322
DOI	10.1038/srep38115
文献子类	Article
英文摘要	SM934 is an artemisinin analogue with immunosuppressive properties and potent therapeutic activity against lupus-like diseases in autoimmune mice. In this report, the therapeutic efficacy and underlying mechanisms of SM934 on rheumatoid arthritis (RA) was investigated using collagen-induced arthritis (CIA) in DBA/1J mice. We demonstrated that SM934 treatment alleviate the severity of arthritis in CIA mice with established manifestations. The therapeutic benefits were associated with ameliorated joint swelling and reduced extent of bone erosion and destruction. Further, administration of SM934 diminished the development of T follicular helper (Tfh) cells and Th17 cells and suppressed the production of pathogenic antibodies, without altering the proportion of germinal center B cells. Ex vivo, SM934 treatment inhibited the bovine type II collagen (CII) induced proliferation and inflammatory cytokines secretion of CII -reactive T cells. In vitro, SM934 impeded the polarization of naive CD4(+) T cells into Tfh cells and the expression of its transcript factor Bcl-6. Moreover, SM934 decreased the IL-21-producing CD4(+) T cells and dampened the IL-21 downstream signaling through STAT3. These finding offered the convincing evidence that artemisinin derivative might attenuate RA by simultaneously interfering with the generation of Tfh cells and Th17 cells as well as the subsequent antibody-mediated immune responses.
资助项目	National Natural Science Foundation of China (NSFC)[81273524] ; National Natural Science Foundation of China (NSFC)[81322049]
WOS关键词	RHEUMATOID-ARTHRITIS ; IMMUNE-RESPONSES ; TH17 CELLS ; DERIVATIVE SM905 ; GERMINAL-CENTERS ; IN-VITRO ; IL-21 ; MICE ; PROLIFERATION ; QINGHAOSU
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000388666900001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275794]
专题	药理学第一研究室
通讯作者	He, Shi-Jun; Tang, Wei; Zuo, Jian-Ping
作者单位	1.Shanghai Univ Tradit Chinese Med, Lab Immunol & Virol, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Lab Immunopharmacol, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Lin, Ze-Min,Yang, Xiao-Qian,Zhu, Feng-Hua,et al. Artemisinin analogue SM934 attenuate collagen-induced arthritis by suppressing T follicular helper cells and T helper 17 cells[J]. SCIENTIFIC REPORTS,2016,6.
APA	Lin, Ze-Min,Yang, Xiao-Qian,Zhu, Feng-Hua,He, Shi-Jun,Tang, Wei,&Zuo, Jian-Ping.(2016).Artemisinin analogue SM934 attenuate collagen-induced arthritis by suppressing T follicular helper cells and T helper 17 cells.SCIENTIFIC REPORTS,6.
MLA	Lin, Ze-Min,et al."Artemisinin analogue SM934 attenuate collagen-induced arthritis by suppressing T follicular helper cells and T helper 17 cells".SCIENTIFIC REPORTS 6(2016).