Autologous Organoid Co-culture Model Reveals T Cell-driven Epithelial Cell Death in Crohn's Disease

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2022 Nov 28

PMID 36439157

Authors

Nassim Hammoudi

Sarah Hamoudi

Julie Bonnereau

Hugo Bottois

Kevin Perez

Madeleine Bezault

Deborah Hassid

Victor Chardiny

Celine Grand

Brice Gergaud

Joelle Bonnet

Leila Chedouba

My-Linh Tran Minh

Jean-Marc Gornet

Clotilde Baudry

Helene Corte

Leon Maggiori

Antoine Toubert

Jacqueline McBride

Camille Brochier

Margaret Neighbors

Lionel Le Bourhis

Matthieu Allez

Affiliations

Soon will be listed here.

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.

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