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- Title
The TNF-family cytokine TL1A drives IL-13-dependent small intestinal inflammation.
- Authors
Meylan, F.; Song, Y.-J.; Fuss, I.; Villarreal, S.; Kahle, E.; Malm, I.-J.; Acharya, K.; Ramos, H. L.; Lo, L.; Mentink-Kane, M. M.; Wynn, T. A.; Migone, T.-S.; Strober, W.; Siegel, R. M.
- Abstract
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.
- Subjects
TUMOR necrosis factors; AUTOIMMUNITY; INFLAMMATORY bowel diseases; T cells; DENDRITIC cells; INTERLEUKINS
- Publication
Mucosal Immunology (1933-0219), 2011, Vol 4, Issue 2, p172
- ISSN
1933-0219
- Publication type
Article
- DOI
10.1038/mi.2010.67