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

doi:10.1016/j.intimp.2022.108702

	Spermine alleviates experimental autoimmune encephalomyelitis via regulating T cell activation and differentiation
	Zheng, Ruting1,2,5 ; Kong, Miaomiao 3; Wang, Siwei 1,2; He, Bingqing1,2,5 ; Xie, Xin1,2,3,4,5,6
	2022-06
发表期刊	INTERNATIONAL IMMUNOPHARMACOLOGY (IF:4.8[JCR-2023],5.0[5-Year])
ISSN	1567-5769
EISSN	1878-1705
卷号	107
发表状态	已发表
DOI	10.1016/j.intimp.2022.108702
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 IFNγ/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 IFNγ/IL17a, IFNγ/IL17a and IFNγ/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.
关键词	EAE ERK MAPK pathway Multiple Sclerosis Polyamines Spermine Th1 Th17
URL	查看原文
收录类别	SCIE ; SCI
语种	英语
资助项目	National Natural Sci-ence Foundation of China[82121005,81730099] ; Shanghai Science and Technology Commission[TM202101H005]
WOS研究方向	Immunology ; Pharmacology & Pharmacy
WOS类目	Immunology ; Pharmacology & Pharmacy
WOS记录号	WOS:000793198400004
出版者	ELSEVIER
Scopus 记录号	2-s2.0-85126476327
来源库	Scopus
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/165041
专题	生命科学与技术学院_博士生生命科学与技术学院_特聘教授组_谢欣组生命科学与技术学院_硕士生
通讯作者	Xie, Xin
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 3.China Pharmaceut Univ, Acad Inst Pharmaceut Sci, Nanjing 210009, Peoples R China 4.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou, Peoples R China 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
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.
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.
MLA	Zheng, Ruting,et al."Spermine alleviates experimental autoimmune encephalomyelitis via regulating T cell activation and differentiation".INTERNATIONAL IMMUNOPHARMACOLOGY 107(2022).