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

Front Immunol. 2022 Nov 10:13:1008456. doi: 10.3389/fimmu.2022.1008456. eCollection 2022.


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: CD103; NKG2D; crohn’s disease; inflammatory bowel diseases; lymphoepithelial interactions; organoids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Coculture Techniques
  • Crohn Disease* / metabolism
  • Epithelial Cells / metabolism
  • Humans
  • Inflammatory Bowel Diseases*
  • Organoids / metabolism