Inhibition of transmethylation down-regulates CD4 T cell activation and curtails development of autoimmunity in a model system

doi:10.4049/jimmunol.178.8.5366

	Inhibition of transmethylation down-regulates CD4 T cell activation and curtails development of autoimmunity in a model system
	Lawson, Brian R.; Manenkova, Yulia ; Ahamed, Jasimuddin ; Chen, Xiaoru ; Zou, Jian-Ping ; Baccala, Roberto ; Theofilopoulos, Argyrios N.; Yuan, Chong
刊名	JOURNAL OF IMMUNOLOGY
	2007-04-15
卷号	178 期号:8 页码:5366-5374
ISSN号	0022-1767
DOI	10.4049/jimmunol.178.8.5366
文献子类	Article
英文摘要	Transmethylation affects several cellular events, including T cell activation, and blockade of this pathway may curtail inflammatory/autoimmune responses. Here, we demonstrate that transmethylation inhibition by a novel reversible S-adenosyl-L-homocysteine hydrolase inhibitor leads to immunosuppression by reducing phosphorylation of several key proteins involved in TCR signaling, including Akt, Erk1/2, and NF-kappa B. Remarkably, this effect was largely restricted to CD4 T cells and correlated with reduced arginine methylation of Vav1, an essential guanine nucleotide exchange factor in T cell stimulation. Treatment with the transmethylation inhibitor averted, and even ameliorated, the CD4-mediated autoimmune disease, experimental autoimmune encephalomyelitis. The data suggest that transmethylation is required for CD4 T cell activation, and its inhibition may be a novel approach in the treatment of multiple sclerosis, and other CD4-mediated autoimmune diseases.
WOS关键词	L-HOMOCYSTEINE HYDROLASE ; S-ADENOSYLHOMOCYSTEINE HYDROLASE ; MULTIPLE-SCLEROSIS ; ARGININE METHYLATION ; ENCEPHALOMYELITIS ; RESPONSES ; PROTEIN ; ADENOSYLMETHIONINE ; INACTIVATION ; PATHOGENESIS
WOS研究方向	Immunology
语种	英语
出版者	AMER ASSOC IMMUNOLOGISTS
WOS记录号	WOS:000245605300082
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273286]
专题	中国科学院上海药物研究所
通讯作者	Lawson, Brian R.
作者单位	1.Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA 2.Gen Atom Co, Diazyme Labs Div, San Diego, CA 92186 USA 3.Shanghai Inst Materia Med, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Lawson, Brian R.,Manenkova, Yulia,Ahamed, Jasimuddin,et al. Inhibition of transmethylation down-regulates CD4 T cell activation and curtails development of autoimmunity in a model system[J]. JOURNAL OF IMMUNOLOGY,2007,178(8):5366-5374.
APA	Lawson, Brian R..,Manenkova, Yulia.,Ahamed, Jasimuddin.,Chen, Xiaoru.,Zou, Jian-Ping.,...&Yuan, Chong.(2007).Inhibition of transmethylation down-regulates CD4 T cell activation and curtails development of autoimmunity in a model system.JOURNAL OF IMMUNOLOGY,178(8),5366-5374.
MLA	Lawson, Brian R.,et al."Inhibition of transmethylation down-regulates CD4 T cell activation and curtails development of autoimmunity in a model system".JOURNAL OF IMMUNOLOGY 178.8(2007):5366-5374.