Autologous organoid co-culture model reveals T cell-driven epithelial cell death in Crohn's Disease.

Autor: Hammoudi, Nassim, Hamoudi, Sarah, Bonnereau, Julie, Bottois, Hugo, Pérez, Kevin, Bezault, Madeleine, Hassid, Déborah, Chardiny, Victor, Grand, Céline, Gergaud, Brice, Bonnet, Joëlle, Chedouba, Leila, My-Linh Tran Minh, Gornet, Jean-Marc, Baudry, Clotilde, Corte, Helène, Maggiori, Léon, Toubert, Antoine, McBride, Jacqueline, Brochier, Camille
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Zdroj: Frontiers in Immunology; 11/10/2022, Vol. 13, p01-16, 16p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index