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

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-

• Grieger, K. M.
• Schröder, V.
• Dehmel, S.
• Neuhaus, V.
• Schaudien, D.
• Fuchs, M.
• Linge, H.
• Wagner, A.
• Kulik, U.
• Gundert, B.
• Aselmann, H.
• Braun, A.
• Hesse, C.
• Sewald, K.