Author:
Hammoudi Nassim,Hamoudi Sarah,Bonnereau Julie,Bottois Hugo,Pérez Kevin,Bezault Madeleine,Hassid Déborah,Chardiny Victor,Grand Céline,Gergaud Brice,Bonnet Joëlle,Chedouba Leila,Tran Minh My-Linh,Gornet Jean-Marc,Baudry Clotilde,Corte Hélène,Maggiori Léon,Toubert Antoine,McBride Jacqueline,Brochier Camille,Neighbors Margaret,Le Bourhis Lionel,Allez Matthieu
Abstract
Lympho-epithelial interactions between intestinal T resident memory cells (Trm) and the epithelium have been associated with inflammatory bowel disease (IBD) activity. We developed ex vivo autologous organoid-mucosal T cell cocultures to functionally assess lymphoepithelial interactions in Crohn’s Disease (CD) patients compared to controls. We demonstrate the direct epithelial cell death induced by autologous mucosal T cells in CD patients but not in controls. These findings were positively correlated with T cell infiltration of the organoids. This potential was inhibited by limiting lympho-epithelial interactions through CD103 and NKG2D blocking antibodies. These data directly demonstrate for the first time the direct deleterious effect of mucosal T cells on the epithelium of CD patients. Such ex-vivo models are promising techniques to unravel the pathophysiology of these diseases and the potential mode of action of current and future therapies.
Funder
Roche
Leona M. and Harry B. Helmsley Charitable Trust
Fondation pour la Recherche Médicale
Subject
Immunology,Immunology and Allergy
Cited by
8 articles.
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