| First Author | Tardif V | Year | 2013 |
| Journal | Clin Immunol | Volume | 147 |
| Issue | 2 | Pages | 133-43 |
| PubMed ID | 23583916 | Mgi Jnum | J:202140 |
| Mgi Id | MGI:5517532 | Doi | 10.1016/j.clim.2013.02.018 |
| Citation | Tardif V, et al. (2013) Critical role of transmethylation in TLR signaling and systemic lupus erythematosus. Clin Immunol 147(2):133-43 |
| abstractText | 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-kappaB 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. |
