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Spermine alleviates experimental autoimmune encephalomyelitis via regulating T cell activation and differentiation

文献类型：期刊论文

作者Zheng, Ruting2,5,6; Kong, Miaomiao4; Wang, Siwei5,6; He, Bingqing2,5,6; Xie, Xin1,2,3,4,5,6
刊名INTERNATIONAL IMMUNOPHARMACOLOGY
出版日期2022-06-01
卷号107页码:11
关键词Spermine Polyamines Multiple Sclerosis EAE Th1 Th17 MAPK pathway ERK
ISSN号1567-5769
DOI10.1016/j.intimp.2022.108702
通讯作者Xie, Xin(xxie@simm.ac.cn)
英文摘要Multiple sclerosis (MS) is a chronic neuroinflammatory disease which causes demyelination, axonal damage and even disability. Th1 and Th17 cells, more precisely, the IFN gamma/IL17a double producing CD4(+) T cells, have been known to play critical roles in the pathogenesis of MS and EAE, a mouse model of MS. Polyamines not only regulate the immune system, but also are essential for the normal function of the central nervous system (CNS). In this study, we demonstrate that the supplementation of spermine (SPM), a biogenic polyamine, significantly suppresses EAE progression in both preventative and therapeutic ways. Further study suggests that spermine significantly reduces IFN gamma(+)/IL17a(-), IFN gamma(-)/IL17a(+) and IFN gamma(+)/IL17a(+) cells in periphery, and thus reducing the infiltration of these pathogenic cells into the CNS. In vitro, spermine has been shown to suppress the activation and proliferation of CD4(+) T cells and also significantly impede the polarization of T effector cells in a dose dependent manner, accompanied by the inhibition of ERK phosphorylation. Consistently, a number of MEK/ ERK inhibitors (including PD0325901, FR180204 and selumetinib) have been found to mimic the effects of spermine in inhibiting CD4(+) T cell activation and T effector cell differentiation. Collectively, spermine alleviates EAE progression by inhibiting CD4(+) T cells activation and T effector cell differentiation in a MAPK/ ERK-dependent manner, suggesting this pathway might be a target to develop effective therapies for MS.
WOS关键词TH17 CELLS ; SIGNAL-TRANSDUCTION ; MEMORY ; TCR ; PATHOGENESIS ; INHIBITION ; POLYAMINES ; THERAPY ; PATHWAY
资助项目National Natural Sci-ence Foundation of China[82121005] ; National Natural Sci-ence Foundation of China[81730099] ; Shanghai Science and Technology Commission[TM202101H005]
WOS研究方向Immunology ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000793198400004
出版者ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/300965]  
专题新药研究国家重点实验室
通讯作者Xie, Xin
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
3.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou, Peoples R China
4.China Pharmaceut Univ, Acad Inst Pharmaceut Sci, Nanjing 210009, Peoples R China
5.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Zheng, Ruting,Kong, Miaomiao,Wang, Siwei,et al. Spermine alleviates experimental autoimmune encephalomyelitis via regulating T cell activation and differentiation[J]. INTERNATIONAL IMMUNOPHARMACOLOGY,2022,107:11.
APA Zheng, Ruting,Kong, Miaomiao,Wang, Siwei,He, Bingqing,&Xie, Xin.(2022).Spermine alleviates experimental autoimmune encephalomyelitis via regulating T cell activation and differentiation.INTERNATIONAL IMMUNOPHARMACOLOGY,107,11.
MLA Zheng, Ruting,et al."Spermine alleviates experimental autoimmune encephalomyelitis via regulating T cell activation and differentiation".INTERNATIONAL IMMUNOPHARMACOLOGY 107(2022):11.

入库方式： OAI收割

来源：上海药物研究所

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