The TNF-family cytokine TL1A drives IL-13-dependent small intestinal inflammation.
Mucosal Immunol
; 4(2): 172-85, 2011 Mar.
Article
en En
| MEDLINE
| ID: mdl-20980995
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Interleucina-13
/
Enteritis
/
Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mucosal Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos