| First Author | Meylan F | Year | 2011 |
| Journal | Mucosal Immunol | Volume | 4 |
| Issue | 2 | Pages | 172-85 |
| PubMed ID | 20980995 | Mgi Jnum | J:267887 |
| Mgi Id | MGI:6270243 | Doi | 10.1038/mi.2010.67 |
| Citation | Meylan F, et al. (2011) The TNF-family cytokine TL1A drives IL-13-dependent small intestinal inflammation. Mucosal Immunol 4(2):172-85 |
| abstractText | The tumor necrosis factor (TNF)-family cytokine TL1A (TNFSF15) costimulates T cells through its receptor DR3 (TNFRSF25) and is required for autoimmune pathology driven by diverse T-cell subsets. TL1A has been linked to human inflammatory bowel disease (IBD), but its pathogenic role is not known. We generated transgenic mice that constitutively express TL1A in T cells or dendritic cells. These mice spontaneously develop IL-13-dependent inflammatory small bowel pathology that strikingly resembles the intestinal response to nematode infections. These changes were dependent on the presence of a polyclonal T-cell receptor (TCR) repertoire, suggesting that they are driven by components in the intestinal flora. Forkhead box P3 (FoxP3)-positive regulatory T cells (Tregs) were present in increased numbers despite the fact that TL1A suppresses the generation of inducible Tregs. Finally, blocking TL1A-DR3 interactions abrogates 2,4,6 trinitrobenzenesulfonic acid (TNBS) colitis, indicating that these interactions influence other causes of intestinal inflammation as well. These results establish a novel link between TL1A and interleukin 13 (IL-13) responses that results in small intestinal inflammation, and also establish that TL1A-DR3 interactions are necessary and sufficient for T cell-dependent IBD. |
