Publication: Vanin-1 licenses inflammatory mediator production by gut epithelial cells and controls colitis by antagonizing peroxisome proliferator-activated receptor γ activity

Publié dans: Journal of Experimental Medicine, 2006, 203 (13), pp.2817-2827. ⟨10.1084/jem/20061640⟩

Auteurs: Carole Berruyer, Laurent Pouyet, Virginie Millet, M. Martin Florent, Aude Legoffic, Alexandra Canonici, Claude Bagnis, Franck Galland, Stephan Garcia, Philippe Naquet

Résumé

Colitis involves immune cell–mediated tissue injuries, but the contribution of epithelial cells remains largely unclear. Vanin-1 is an epithelial ectoenzyme with a pantetheinase activity that provides cysteamine/cystamine to tissue. Using the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-colitis model we show here that Vanin-1 deficiency protects from colitis. This protection is reversible by administration of cystamine or bisphenol A diglycidyl ether, a peroxisome proliferator-activated receptor (PPAR) 후 antagonist. We further demonstrate that Vanin-1, by antagonizing PPAR 후, licenses the production of inflammatory mediators by intestinal epithelial cells. We propose that Vanin-1 is an epithelial sensor of stress that exerts a dominant control over innate immune responses in tissue. Thus, the Vanin-1/ pantetheinase activity might be a new target for therapeutic intervention in infl ammatory bowel disease.

Lien vers HAL – hal-01076821

Lien vers le DOI – 10.1084/jem/20061640