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

**Authors:** Meg Nakazawa, Itsuma Nagao, Yoko M. Ambrosini

PMC · DOI: 10.1186/s12860-025-00536-w · BMC Molecular and Cell Biology · 2025-04-08

## TL;DR

This study uses canine intestinal organoids to explore how immune-related MHC class II molecules are expressed in gut cells, especially under inflammatory conditions.

## Contribution

The study introduces canine intestinal organoids as a novel in vitro model for investigating MHC class II expression in immune-mediated gastrointestinal diseases.

## Key findings

- Canine colonoids from healthy dogs showed increased MHC class II and CIITA expression after IFN-γ treatment.
- MHC class II induction was stronger in differentiated colonoids cultured without Wnt-3a.
- The model highlights the role of intestinal epithelial cells in immune responses during inflammation.

## Abstract

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.

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.

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.

The online version contains supplementary material available at 10.1186/s12860-025-00536-w.

## Linked entities

- **Genes:** CIITA (class II major histocompatibility complex transactivator) [NCBI Gene 4261]
- **Proteins:** IFNG (interferon gamma), WNT3A (Wnt family member 3A)
- **Diseases:** inflammatory bowel disease (MONDO:0005265)
- **Species:** Canis lupus familiaris (taxon 9615)

## Full-text entities

- **Genes:** CIITA (class II major histocompatibility complex transactivator) [NCBI Gene 490008], CD4 (CD4 molecule) [NCBI Gene 403931], IFNG (interferon gamma) [NCBI Gene 403801] {aka IFN-G, IFN-gamma}, WNT3A (Wnt family member 3A) [NCBI Gene 482208]
- **Diseases:** inflammatory (MESH:D007249), gastrointestinal diseases (MESH:D005767), IBD (MESH:D015212)
- **Species:** gut metagenome (species) [taxon 749906], Canis lupus familiaris (dog, subspecies) [taxon 9615]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11980282/full.md

## References

12 references — full list in the complete paper: https://tomesphere.com/paper/PMC11980282/full.md

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Source: https://tomesphere.com/paper/PMC11980282