Critical role of transmethylation in TLR signaling and systemic lupus erythematosus.
Critical role of transmethylation in TLR signaling and systemic lupus erythematosus.
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DOI：
10.1016/j.clim.2013.02.018
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发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Lawson BR
中科院分区：
文献类型：
--
作者：
Tardif V;Manenkova Y;Berger M;Hoebe K;Zuo JP;Yuan C;Kono DH;Theofilopoulos AN;Lawson BR
Post-translational protein modifications can play a significant role in immune cell signaling. Recently, we showed that inhibition of transmethylation curtails experimental autoimmune encephalomyelitis, notably by reducing T cell receptor (TCR)-induced activation of CD4+ T cells. Here, we demonstrate that transmethylation inhibition by a reversible S-adenosyl-l-homocysteine hydrolase inhibitor (DZ2002) led to immunosuppression by reducing TLR-, B cell receptor (BCR)- and TCR-induced activation of immune cells, most likely by blocking NF-κB activity. Moreover, prophylactic treatment with DZ2002 prevented lupus-like disease from developing in both BXSB and MRL-Faslpr mouse models. DZ2002 treatment initiated during active disease significantly improved outcomes in both in vivo models, suggesting methylation inhibition as a novel approach for the treatment of autoimmune/inflammatory diseases.
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