| First Author | Siebler J | Year | 2008 |
| Journal | J Immunol | Volume | 180 |
| Issue | 1 | Pages | 30-3 |
| PubMed ID | 18096999 | Mgi Jnum | J:130899 |
| Mgi Id | MGI:3772520 | Doi | 10.4049/jimmunol.180.1.30 |
| Citation | Siebler J, et al. (2008) Cutting edge: a key pathogenic role of IL-27 in T cell- mediated hepatitis. J Immunol 180(1):30-3 |
| abstractText | The signals driving T cell activation in T cell-mediated fulminant hepatitis are not fully understood. In this study, we identify the cytokine IL-27p28/EBI3 as a major pathogenic factor in the ConA model of T cell-mediated hepatitis. We found an up-regulation of hepatic EBI3 and p28 expression and augmented levels of IL-27 in wild-type mice after ConA administration, suggesting a potential pathogenic role of this cytokine in ConA hepatitis. Consistently, IL-27 EBI3-deficient mice were almost completely protected from ConA-induced liver damage. Such protection was associated with reduced levels of IFN-gamma and its signaling proteins pSTAT-1 and T-bet. Finally, in vivo blockade of IL-27 function using a soluble IL-27 receptor fusion protein led to reduced pSTAT1 levels and suppression of liver injury. Taken together, these data demonstrate a key pathogenic role of IL-27 in T cell-mediated liver injury. Furthermore, in vivo blockade of IL-27 emerges as a novel potential therapy for T cell-mediated hepatitis. |
