ArticleClinical immunology (Orlando, Fla.)2013
Critical role of transmethylation in TLR signaling and systemic lupus erythematosus.
Article in Clinical immunology (Orlando, Fla.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Protein Arginine Methyltransferase 5 in T Lymphocyte Biology.Trends in immunology · 2020Review
- DZ2002 ameliorates fibrosis, inflammation, and vasculopathy in experimental systemic sclerosis models.Arthritis research & therapy · 2019Article
- Reversible SAHH inhibitor protects against glomerulonephritis in lupus-prone mice by downregulating renal α-actinin-4 expression and stabilizing integrin-cytoskeleton linkage.Arthritis research & therapy · 2019Article
- Time-resolved metabolomics analysis of individual differences during the early stage of lipopolysaccharide-treated rats.Scientific reports · 2016Article
- Suppressive effects of tumor cell-derived 5'-deoxy-5'-methylthioadenosine on human T cells.Oncoimmunology · 2016Article
- Toll-like receptors: potential targets for lupus treatment.Acta pharmacologica Sinica · 2015Review
- Therapeutic effects of DZ2002, a reversible SAHH inhibitor, on lupus-prone NZB×NZW F1 mice via interference with TLR-mediated APC response.Acta pharmacologica Sinica · 2014Article
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Authors and funding
9 authors.
Funding
Abstract
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-Fas(lpr) 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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