| First Author | Schramm C | Year | 2003 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 284 |
| Issue | 3 | Pages | G525-35 |
| PubMed ID | 12466145 | Mgi Jnum | J:82485 |
| Mgi Id | MGI:2653396 | Doi | 10.1152/ajpgi.00286.2002 |
| Citation | Schramm C, et al. (2003) Impairment of TGF-beta signaling in T cells increases susceptibility to experimental autoimmune hepatitis in mice. Am J Physiol Gastrointest Liver Physiol 284(3):G525-35 |
| abstractText | In autoimmune hepatitis, strong TGF-beta1 expression is found in the inflamed liver. TGF-beta overexpression may be part of a regulatory immune response attempting to suppress autoreactive T cells. To test this hypothesis, we determined whether impairment of TGF-beta signaling in T cells leads to increased susceptibility to experimental autoimmune hepatitis (EAH). Transgenic mice of strain FVB/N were generated expressing a dominant-negative TGF-beta type II receptor in T cells under the control of the human CD2 promoter/locus control region. On induction of EAH, transgenic mice showed markedly increased portal and periportal leukocytic infiltrations with hepatocellular necroses compared with wild-type mice (median histological score = 1.8 +/- 0.26 vs. 0.75 +/- 0.09 in wild-type mice; P < 0.01). Increased IFN-gamma production (118 vs. 45 ng/ml) and less IL-4 production (341 vs. 1,256 pg/ml) by mononuclear cells isolated from transgenic livers was seen. Impairment of TGF-beta signaling in T cells therefore leads to increased susceptibility to EAH in mice. This suggests an important role for TGF-beta in immune homeostasis in the liver and may teleologically explain TGF-beta upregulation in response to T cell-mediated liver injury. |
