| First Author | Lovett-Racke AE | Year | 2004 |
| Journal | Immunity | Volume | 21 |
| Issue | 5 | Pages | 719-31 |
| PubMed ID | 15539157 | Mgi Jnum | J:93885 |
| Mgi Id | MGI:3510073 | Doi | 10.1016/j.immuni.2004.09.010 |
| Citation | Lovett-Racke AE, et al. (2004) Silencing T-bet defines a critical role in the differentiation of autoreactive T lymphocytes. Immunity 21(5):719-31 |
| abstractText | As a means of developing therapies that target the pathogenic T cells in multiple sclerosis (MS) without compromising the immune system or eliciting systemic side effects, we investigated the use of T-bet-specific antisense oligonucleotides and small interfering RNAs (siRNA) to silence T-bet expression in autoreactive encephalitogenic T cells and evaluated the biological consequences of this suppression in experimental autoimmune encephalomyelitis, a model for MS. The T-bet-specific AS oligonucleotide and siRNA suppressed T-bet expression, IFNgamma production, and STAT1 levels during antigen-specific T cell differentiation. In vitro suppression of T-bet during differentiation of myelin-specific T cells and in vivo administration of a T-bet-specific antisense oligonucleotide or siRNA inhibited disease. T-bet was shown to bind the IFNgamma and STAT1 promoters, but did not regulate the IL-12/STAT4 pathway. Since T-bet regulates IFNgamma production in CD4(+) T cells, but to a lesser extent in most other IFNgamma-producing cells, T-bet may be a target for therapeutics for Th1-mediated diseases. |
