Spatial immunoprofiling of human colon in health and disease: insights into inflammation 2256907

Abstract

Abstract Introduction Inflammatory bowel diseases (IBD) are chronic, relapsing inflammatory conditions of the gastrointestinal tract. Despite advances in understanding their pathogenesis, challenges remain in diagnosis, treatment, and long-term management [1]. Their clinical heterogeneity, variable therapeutic response, and lack of reliable biomarkers, underscore the need for improved spatial and molecular characterization of immune mechanisms to uncover pathophysiological processes and identify potential therapeutic targets [2]. Here we leveraged automated multiplex sequential immunofluorescence (seqIF™) [3] to spatially profile protein expression and cellular interactions across a spectrum of colon pathologies. Methods A tissue microarray comprising Crohn’s disease, ulcerative colitis, chronic colonic inflammation, neoplastic lesions, and normal colon tissues was stained and imaged on the COMET™ platform. Multiplexed images were analyzed at single-cell spatial resolution using HORIZON™ software. Results The high-plex proteomics panel enabled the simultaneous detection of over 60 biomarkers on the same tissue slide, allowing an in-depth characterization of inflammatory responses and mucosal remodeling associated with inflammatory colon pathologies. This spatial profiling of the tissue microenvironment revealed the cellular heterogeneity, stromal interactions, and a robust immune cell activation across diverse types of IBD. Conclusion These results provide a broad view of the complex cellular mechanisms underlying IBD. Automated high-plex immunophenotyping offers novel insights into immune cell dynamics and tissue organization, potentially guiding precision therapeutic strategies in colonic inflammation. References Selin et al. J Crohns Colitis. 2021 May 7;15(11):1959—1973. Zheng et al. J Inflamm Res. 2025 Jul 9:18:8977-8992. Rivest F et al. Sci Rep. 2023. 13(1):16994. Funding Source n/a Topic Categories Immune Mechanisms of Human Disease (HUM)