| First Author | Wirtz S | Year | 1999 |
| Journal | J Immunol | Volume | 162 |
| Issue | 4 | Pages | 1884-8 |
| PubMed ID | 9973454 | Mgi Jnum | J:124432 |
| Mgi Id | MGI:3721504 | Doi | 10.4049/jimmunol.162.4.1884 |
| Citation | Wirtz S, et al. (1999) Cutting edge: chronic intestinal inflammation in STAT-4 transgenic mice: characterization of disease and adoptive transfer by TNF- plus IFN-gamma-producing CD4+ T cells that respond to bacterial antigens. J Immunol 162(4):1884-8 |
| abstractText | We generated transgenic mice for STAT-4, a regulatory protein specifically associated with IL-12 signaling, under the control of a CMV promoter. These mice expressed strikingly increased nuclear STAT-4 levels in lamina propria CD4+ T lymphocytes upon systemic administration of dinitrophenyl-keyhole limpet hemocyanin and developed chronic transmural colitis characterized by infiltrates of mainly CD4+ T lymphocytes. The latter cells produced predominantly TNF and IFN-gamma but not IL-4 upon activation with alphaCD3/CD28 or autologous bacterial Ags, consistent with a Th1-type cell response. Furthermore, chronic colitis in STAT-4 transgenic mice could be adoptively transferred to SCID mice by colonic and splenic CD4+ T cells that were activated with Ags from autologous bacterial flora. These data establish a critical molecular signaling pathway involving STAT-4 for the pathogenesis of chronic intestinal inflammation, and targeting of this pathway may be relevant for the treatment of colitis in humans. |
