Frontiers in Immunology (Nov 2022)
Autologous organoid co-culture model reveals T cell-driven epithelial cell death in Crohn’s Disease
- Nassim Hammoudi,
- Nassim Hammoudi,
- Sarah Hamoudi,
- Julie Bonnereau,
- Hugo Bottois,
- Kevin Pérez,
- Madeleine Bezault,
- Déborah Hassid,
- Déborah Hassid,
- Victor Chardiny,
- Céline Grand,
- Brice Gergaud,
- Joëlle Bonnet,
- Leila Chedouba,
- My-Linh Tran Minh,
- Jean-Marc Gornet,
- Clotilde Baudry,
- Hélène Corte,
- Léon Maggiori,
- Antoine Toubert,
- Jacqueline McBride,
- Camille Brochier,
- Margaret Neighbors,
- Lionel Le Bourhis,
- Matthieu Allez,
- Matthieu Allez
Affiliations
- Nassim Hammoudi
- Université de Paris, INSERM U1160, EMiLy, Institut de Recherche Saint-Louis, Paris, France
- Nassim Hammoudi
- Gastroenterology Department, AP-HP, Hôpital Saint-Louis/Lariboisière, Paris, France
- Sarah Hamoudi
- Université de Paris, INSERM U1160, EMiLy, Institut de Recherche Saint-Louis, Paris, France
- Julie Bonnereau
- Université de Paris, INSERM U1160, EMiLy, Institut de Recherche Saint-Louis, Paris, France
- Hugo Bottois
- Université de Paris, INSERM U1160, EMiLy, Institut de Recherche Saint-Louis, Paris, France
- Kevin Pérez
- Université de Paris, INSERM U1160, EMiLy, Institut de Recherche Saint-Louis, Paris, France
- Madeleine Bezault
- Université de Paris, INSERM U1160, EMiLy, Institut de Recherche Saint-Louis, Paris, France
- Déborah Hassid
- Université de Paris, INSERM U1160, EMiLy, Institut de Recherche Saint-Louis, Paris, France
- Déborah Hassid
- Gastroenterology Department, AP-HP, Hôpital Saint-Louis/Lariboisière, Paris, France
- Victor Chardiny
- Université de Paris, INSERM U1160, EMiLy, Institut de Recherche Saint-Louis, Paris, France
- Céline Grand
- Université de Paris, INSERM U1160, EMiLy, Institut de Recherche Saint-Louis, Paris, France
- Brice Gergaud
- Université de Paris, INSERM U1160, EMiLy, Institut de Recherche Saint-Louis, Paris, France
- Joëlle Bonnet
- Gastroenterology Department, AP-HP, Hôpital Saint-Louis/Lariboisière, Paris, France
- Leila Chedouba
- Gastroenterology Department, AP-HP, Hôpital Saint-Louis/Lariboisière, Paris, France
- My-Linh Tran Minh
- Gastroenterology Department, AP-HP, Hôpital Saint-Louis/Lariboisière, Paris, France
- Jean-Marc Gornet
- Gastroenterology Department, AP-HP, Hôpital Saint-Louis/Lariboisière, Paris, France
- Clotilde Baudry
- Gastroenterology Department, AP-HP, Hôpital Saint-Louis/Lariboisière, Paris, France
- Hélène Corte
- Digestive Surgery Department, AP-HP, Hôpital Saint-Louis/Lariboisière, Paris, France
- Léon Maggiori
- Digestive Surgery Department, AP-HP, Hôpital Saint-Louis/Lariboisière, Paris, France
- Antoine Toubert
- Université de Paris, INSERM U1160, EMiLy, Institut de Recherche Saint-Louis, Paris, France
- Jacqueline McBride
- OMNI Biomarker Development, Genentech Inc., South San Francisco, CA, United States
- Camille Brochier
- Ile de France, Institut Roche, Boulogne-Billancourt, France
- Margaret Neighbors
- OMNI Biomarker Development, Genentech Inc., South San Francisco, CA, United States
- Lionel Le Bourhis
- Université de Paris, INSERM U1160, EMiLy, Institut de Recherche Saint-Louis, Paris, France
- Matthieu Allez
- Université de Paris, INSERM U1160, EMiLy, Institut de Recherche Saint-Louis, Paris, France
- Matthieu Allez
- Gastroenterology Department, AP-HP, Hôpital Saint-Louis/Lariboisière, Paris, France
- DOI
- https://doi.org/10.3389/fimmu.2022.1008456
- Journal volume & issue
-
Vol. 13
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.
Keywords
