RT Journal Article
SR Electronic
T1 Nod2 protects remote small intestinal sites in case of colonic inflammation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 510933
DO 10.1101/510933
A1 Ziad Al Nabhani
A1 Dominique Berrebi
A1 Christine Martinez-Vinson
A1 Nicolas Montcuquet
A1 Gilles Dietrich
A1 Gurminder Singh
A1 Jerrold R. Turner
A1 Chrystele Madre
A1 Maryline Roy
A1 Eric Ogier-Denis
A1 Monique Dussaillant
A1 Nadine Cerf-Bensussan
A1 Habib Zouali
A1 Camille Jung
A1 Fanny Daniel
A1 Frédérick Barreau
A1 Jean-Pierre Hugot
YR 2019
UL http://biorxiv.org/content/early/2019/01/03/510933.abstract
AB 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 pro-inflammatory cytokine expression, recirculating CD4+ 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.AbbreviationsCDCrohn’s diseaseIMintestinal mucosa (without Peyer’s patches)MDPMuramyl dipeptideMLCKmyosin light chain kinaseNOD2nucleotide oligomerization domain 2RICKreceptor-interacting serine/threonine kinaseTAK1transforming growth factor β-activated kinase 1TNBS2,4,6-trinitrobenzene sulfonic acidTNF-RTNF receptorWTwild-type