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 TITLE=Autologous organoid co-culture model reveals T cell-driven epithelial cell death in Crohn’s Disease JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1008456 DOI=10.3389/fimmu.2022.1008456 ISSN=1664-3224 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.