Canine intestinal organoids as a platform for studying MHC class II expression in epithelial cells.

Abstract

Backgrounds: The interplay between intestinal epithelial cells (IECs), the immune system, and the gut microbiome is pivotal for maintaining gastrointestinal homeostasis and mediating responses to ingested antigens. IECs, capable of expressing Major Histocompatibility Complex (MHC) class II molecules, are essential in modulating immune responses, especially CD4 + T cells, in both physiological and pathological contexts. The expression of MHC class II on IECs, regulated by the class II transactivator (CIITA) and inducible by cytokine IFN-γ, has been traditionally associated with professional antigen-presenting cells but is now recognized in the context of inflammatory conditions such as inflammatory bowel disease (IBD). In veterinary medicine, particularly among canine populations, MHC (or Dog Leukocyte Antigen, DLA) expression on IECs underlines its significance in intestinal immune pathologies, yet remains underexplored. This study aims to leverage canine intestinal organoids as a novel in vitro model to elucidate MHC class II expression dynamics and their implications in immune-mediated gastrointestinal diseases, bridging the gap between basic research and clinical application in canine health.

Results: Canine colonoids derived from healthy dogs showed significant expression of MHC class II and its promoter gene, CIITA, after IFN-γ treatment. This MHC class II induction was even more pronounced in differentiated colonoids cultured in Wnt-3a-depleted medium.

Conclusions: This study provides insights into the role of IECs as antigen-presenting cells and demonstrates the use of intestinal organoids for investigating epithelial immune responses in inflammatory conditions.