# Ex Vivo Modeling and Pharmacological Modulation of Tissue Immune Responses in Inflammatory Bowel Disease Using Precision‐Cut Intestinal Slices

## TL;DR

Researchers used intestinal tissue slices from IBD patients to study immune responses and test drug effects in a lab setting, offering a new way to understand and treat inflammatory bowel disease.

## Contribution

The study introduces precision-cut intestinal slices as a novel ex vivo model to study immune responses and drug effects in IBD patient tissue.

## Key findings

- IBD-derived intestinal slices showed immune infiltration and upregulated inflammatory pathways.
- IBD tissue released higher cytokine levels in response to immune stimuli compared to non-IBD tissue.
- Pimecrolimus reduced cytokine release and improved tissue integrity in IBD slices.

## Abstract

Inflammatory bowel disease (IBD) affects approximately 5 million people worldwide, causing chronic inflammation and increased mortality. Despite advances in therapy, the underlying immune mechanisms remain poorly understood, highlighting the need for human‐immunocompetent models to enhance translational research. This study aimed to investigate local immune responses using precision‐cut intestinal slices (PCIS) from IBD patients and evaluate immunomodulatory treatment directly in patient tissue ex vivo. PCIS from ileal resections of IBD and non‐IBD patients were stimulated with Concanavalin A (ConA) or lipopolysaccharide (LPS). Histological analysis of IBD‐derived PCIS showed villus atrophy, infiltration of lymphocytes and macrophages, and RNA analysis revealed upregulation of IL‐17 and interferon signaling pathways. LPS‐ and ConA‐induced functional immune responses in the tissue, with IBD tissue exhibiting increased levels of specific cytokines compared with non‐IBD tissue, including IL‐17F and IL‐21 after ConA‐stimulation, and IL‐22 as well as ENA‐78 following LPS‐stimulation. Pimecrolimus treatment led to a marked reduction in the release of IL‐2, IL‐17A, and IFN‐γ, and inhibited the IBD supernatant‐induced reduction in transepithelial electrical resistance. Our data provide the first in‐depth characterization of local tissue immune responses in human PCIS, highlighting the potential of this model to study disease‐specific immune activity and evaluate pharmacological interventions ex vivo.

Studying local immune responses in IBD remains challenging. This study demonstrates that precision‐cut intestinal slices from IBD patients mimic key immunopathological features ex vivo and respond specifically to immune stimuli. This model allows direct pharmacological modulation of patient tissue ex vivo and offers a powerful platform for translational research.