Nod2 protects remote small intestinal sites in case of colonic inflammation. - Université Paris Cité Accéder directement au contenu
Pré-Publication, Document De Travail (Preprint/Prepublication) Année : 2019

Nod2 protects remote small intestinal sites in case of colonic inflammation.

Ziad Al Nabhani
  • Fonction : Auteur
Gilles Dietrich
Maryline Roy
  • Fonction : Auteur
Eric Ogier-Denis
  • Fonction : Auteur

Résumé

NOD2 mutations are key risk factors for Crohn’s disease (CD). NOD2 contributes to intestinal homeostasis by regulating innate and adaptive immunity together with intestinal epithelial function. However, the roles of NOD2 during gut inflammation is not known. We initially observed that NOD2 expression was increased in epithelial cells remote from inflamed areas in CD patients. To explore this finding, Nod2 mRNA expression, inflammation and gut permeability were examined in the small bowel of wild-type (WT), Nod2 knockout and Nod2 mutant mice after rectal instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS). In WT mice, Nod2 upregulation remote to rectal injury was associated with proinflammatory cytokine expression, recirculating CD4+ 46 T-cells, increased paracellular permeability and myosin like chain kinase activity. Nod2 knockout or mutation led to duodenitis and ileitis demonstrating the remote protective role of Nod2. Bone morrow stem cell (BMSC) transplantations indicated that the small intestinal inflammation was due to NOD2 loss in both hematopoietic and non-hematopoietic compartments. As a whole, WT but not mutant NOD2 prevents disease extension at sites remote from the initial intestinal injury.
Fichier principal
Vignette du fichier
Al Nabhan-BioArxiv-2019_1.pdf (6.83 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

hal-02790129 , version 1 (05-06-2020)

Licence

Paternité - Pas d'utilisation commerciale - Pas de modification

Identifiants

Citer

Jean-Pierre Hugot, Ziad Al Nabhani, Dominique Berrebi, Christine Martinez-Vinson, Nicolas Montcuquet, et al.. Nod2 protects remote small intestinal sites in case of colonic inflammation.. 2019. ⟨hal-02790129⟩
57 Consultations
61 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More