Abstract Background The IL-33/ST2 signalling pathway is an important mediator of mucosal immunity and epithelial barrier homeostasis. However, its distribution within inflammatory bowel disease (IBD) tissues—across both Crohn’s disease (CD) and ulcerative colitis (UC)—is still not fully delineated, particularly with respect to anatomical site and disease phenotype. Methods Thirty-one intestinal mucosal biopsies from patients with Crohn’s disease (CD) or ulcerative colitis (UC) were analysed. Samples were collected from different anatomical regions, including the ileum, right and left colon, and rectum. Immunofluorescence staining was performed through sequential incubation with primary antibodies against IL-33 or ST2, followed by fluorophore-conjugated secondary antibodies. Nuclei were counterstained with a DNA-binding fluorescent dye. Confocal images were acquired at 20× magnification. IL-33 and ST2 expression were assessed visually on a semi-quantitative 1–9 scale by two independent, blinded observers. Statistical analyses included Spearman correlation, Mann–Whitney U, and Kruskal–Wallis tests. Results IL-33 and ST2 scores were significantly correlated (r = 0.54, p = 0.002), indicating coordinated expression within the mucosa. IL-33 levels were significantly higher in CD than in UC (p = 0.038), while ST2 levels did not differ between diagnoses (p = 0.558). IL-33 expression also varied significantly with biopsy location (p 0.05), with the highest scores observed in ileal samples. No significant differences were found in IL-33 or ST2 expression based on patient sex or biologic treatment exposure. These findings suggest a site- and disease-specific modulation of IL-33 expression, independent of systemic factors. Conclusion This study highlights a consistent co-expression of IL-33 and ST2 in the mucosa of IBD patients, with IL-33 levels significantly increased in Crohn’s disease and exhibiting regional variation along the gastrointestinal tract. These findings underscore the biological importance of the IL-33/ST2 axis in the immune landscape of IBD and pave the way for future research into its mechanistic and clinical implications. This work was supported by the Ministry of University and Research, Italy, PRIN project number 20228Z74LP “TOPmodHEAL-IBD” Conflict of interest: Mr. Pane, Cesare: No conflict of interest Di Mattia, Miriam: No conflict of interest Petito, Valentina: No conflict of interest Capobianco, Ivan: No Conflict of interest to declare Foscarini, Elisa: NA Profeta, Francesca: NA Del Pizzo, Francesco: No conflict of interest Troisi, Sara: No conflict of interest Migliore, Greta: No conflict of interest Gasbarrini, Antonio: No conflict of interest Scaldaferri, Franco: No conflict of interest Lopetuso, Loris Riccardo: No conflict of interest
Pane et al. (Thu,) studied this question.