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	Lrch1 interferes with dock8-cdc42-induced t cell migration and ameliorates experimental autoimmune encephalomyelitis
	Xu, Xiaoyan1; Han, Lei1; Zhao, Guixian5; Xue, Shengjie1; Gao, Yunzhen1; Xiao, Jun1; Zhang, Shicheng3,4; Chen, Peng1; Wu, Zhi-ying7,8; Ding, Jianping3,4
刊名	Journal of experimental medicine
	2017
卷号	214期号:1页码:209-226
ISSN号	0022-1007
DOI	10.1084/jem.20160068
通讯作者	Wang, hongyan(hongyanwang@sibcb.ac.cn)
英文摘要	Directional autoreactive cd4(+) t cell migration into the central nervous system plays a critical role in multiple sclerosis. recently, dock8 was identified as a guanine-nucleotide exchange factor (gef) for cdc42 activation and has been associated with human mental retardation. little is known about whether dock8 is related to multiple sclerosis (ms) and how to restrict its gef activity. using two screening systems, we found that lrch1 competes with cdc42 for interaction with dock8 and restrains t cell migration. in response to chemokine stimulation, pkca phosphorylates dock8 at its three serine sites, promoting dock8 separation from lrch1 and translocation to the leading edge to guide t cell migration. point mutations at the dock8 serine sites block chemokine-and pkc alpha-induced t cell migration. importantly, dock8 mutant mice or lrch1 transgenic mice were protected from mog (35-55) peptide-induced experimental autoimmune encephalomyelitis (eae), whereas lrch1-deficient mice displayed a more severe phenotype. notably, dock8 expression was markedly increased in pbmcs from the acute phase of ms patients. together, our study demonstrates lrch1 as a novel effector to restrain pkc alpha-dock8-cdc42 module-induced t cell migration and ameliorate eae.
WOS关键词	CENTRAL-NERVOUS-SYSTEM ; MULTIPLE-SCLEROSIS SUSCEPTIBILITY ; OSTEOARTHRITIS SUSCEPTIBILITY ; ADHESION MOLECULES ; IMMUNE-RESPONSES ; DOCK8 MUTATIONS ; ACTIVATION ; INTEGRIN ; CDC42 ; BINDING
WOS研究方向	Immunology ; Research & Experimental Medicine
WOS类目	Immunology ; Medicine, Research & Experimental
语种	英语
出版者	ROCKEFELLER UNIV PRESS
WOS记录号	WOS:000391123600016
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2373481
专题	武汉病毒研究所
通讯作者	Wang, Hongyan
作者单位	1.Univ Chinese Acad Sci, CAS, CAS Ctr Excellence Mol Cell Sci, Key Lab Syst Biol,Innovat Ctr Cell Signaling Netw, Shanghai 200031, Peoples R China 2.Univ Chinese Acad Sci, CAS, Shanghai Inst Biol Sci, State Key Lab Cell Biol,Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China 3.Univ Chinese Acad Sci, CAS, Natl Ctr Prot Sci Shanghai, Shanghai 201203, Peoples R China 4.Univ Chinese Acad Sci, CAS, State Key Lab Biochem, Shanghai 201203, Peoples R China 5.Fudan Univ, HuaShan Hosp, Shanghai 200031, Peoples R China 6.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan 430071, Peoples R China 7.Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Neurol, Hangzhou 310009, Zhejiang, Peoples R China 8.Zhejiang Univ, Sch Med, Affiliated Hosp 2, Res Ctr Neurol, Hangzhou 310009, Zhejiang, Peoples R China
推荐引用方式 GB/T 7714	Xu, Xiaoyan,Han, Lei,Zhao, Guixian,et al. Lrch1 interferes with dock8-cdc42-induced t cell migration and ameliorates experimental autoimmune encephalomyelitis[J]. Journal of experimental medicine,2017,214(1):209-226.
APA	Xu, Xiaoyan.,Han, Lei.,Zhao, Guixian.,Xue, Shengjie.,Gao, Yunzhen.,...&Wang, Hongyan.(2017).Lrch1 interferes with dock8-cdc42-induced t cell migration and ameliorates experimental autoimmune encephalomyelitis.Journal of experimental medicine,214(1),209-226.
MLA	Xu, Xiaoyan,et al."Lrch1 interferes with dock8-cdc42-induced t cell migration and ameliorates experimental autoimmune encephalomyelitis".Journal of experimental medicine 214.1(2017):209-226.

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