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Intestinal epithelial expression of TNFAIP3 results in microbial invasion of the inner mucus layer and induces colitis in IL-10-deficient mice.
Murphy, Stephen F; Rhee, Lesley; Grimm, Wesley A; Weber, Christopher R; Messer, Jeannette S; Lodolce, James P; Chang, Jonathan E; Bartulis, Sarah J; Nero, Thomas; Kukla, Renata A; MacDougall, Gordon; Binghay, Charles; Kolodziej, Lauren E; Boone, David L.
Afiliación
  • Murphy SF; Department of Medicine, University of Chicago, Chicago, Illinois;
  • Rhee L; Department of Medicine, University of Chicago, Chicago, Illinois;
  • Grimm WA; Department of Medicine, University of Chicago, Chicago, Illinois;
  • Weber CR; Department of Pathology, University of Chicago, Chicago, Illinois;
  • Messer JS; Department of Medicine, University of Chicago, Chicago, Illinois;
  • Lodolce JP; Department of Medicine, University of Chicago, Chicago, Illinois;
  • Chang JE; Department of Medicine, University of Chicago, Chicago, Illinois;
  • Bartulis SJ; Department of Medicine, University of Chicago, Chicago, Illinois;
  • Nero T; Department of Medicine, University of Chicago, Chicago, Illinois;
  • Kukla RA; Department of Medicine, University of Chicago, Chicago, Illinois;
  • MacDougall G; Indiana University School of Medicine, South Bend, Indiana.
  • Binghay C; Indiana University School of Medicine, South Bend, Indiana.
  • Kolodziej LE; Department of Medicine, University of Chicago, Chicago, Illinois;
  • Boone DL; Indiana University School of Medicine, South Bend, Indiana daboone@iu.edu.
Am J Physiol Gastrointest Liver Physiol ; 307(9): G871-82, 2014 Nov 01.
Article en En | MEDLINE | ID: mdl-25234043
Tumor necrosis factor-induced protein 3 (TNFAIP3; also known as A20) negatively regulates NF-κB and MAPK signals to control inflammatory responses. TNFAIP3 also protects against TNF-induced cell death. Intestinal epithelial cell (IEC) expression of TNFAIP3 improves barrier function and tight junction integrity and prevents dextran sulfate sodium (DSS)-induced IEC death and colitis. We therefore investigated the effects of TNFAIP3 expression in IEC on immune homeostasis in the intestines of immune-compromised mice. Villin-TNFAIP3 (v-TNFAIP3) transgenic mice were interbred with IL-10(-/-) mice (v-TNFAIP3 × IL-10(-/-)) and incidence, onset, and severity of colitis was assessed. v-TNFAIP3 × IL-10(-/-) mice displayed severe, early onset, and highly penetrant colitis that was not observed in IL-10(-/-) or v-TNFAIP3 mice. V-TNFAIP3 mice displayed altered expression of mucosal cytokines, increased numbers of mucosal regulatory T cells, and altered expression of mucosal antimicrobial peptides (AMPs). Microbial colonization of the inner mucus layer of v-TNFAIP3 mice was observed, along with alterations in the microbiome, but this was not sufficient to induce colitis in v-TNFAIP3 mice. The relative sterility of the inner mucus layer observed in wild-type and IL-10(-/-) mice was lost in v-TNFAIP3 × IL-10(-/-) mice. Thus IEC-derived factors, induced by signals that are inhibited by TNFAIP3, suppress the onset of inflammatory bowel disease in IL-10(-/-) mice. Our results indicate that IEC expression of TNFAIP3 alters AMP expression and allows microbial colonization of the inner mucus layer, which activates an IL-10-dependent anti-inflammatory process that is necessary to prevent colitis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cisteína Endopeptidasas / Colitis Ulcerosa / Interleucina-10 / Péptidos y Proteínas de Señalización Intracelular / Microbiota / Mucosa Intestinal Límite: Animals Idioma: En Revista: Am J Physiol Gastrointest Liver Physiol Asunto de la revista: FISIOLOGIA / GASTROENTEROLOGIA Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cisteína Endopeptidasas / Colitis Ulcerosa / Interleucina-10 / Péptidos y Proteínas de Señalización Intracelular / Microbiota / Mucosa Intestinal Límite: Animals Idioma: En Revista: Am J Physiol Gastrointest Liver Physiol Asunto de la revista: FISIOLOGIA / GASTROENTEROLOGIA Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos