Reveal the key mediators of inflammation in Crohn's disease undergoing biological treatments

Crohn’s disease (CD) is a major subtype of life-long Inflammatory Bowel Disease (IBD) affecting a growing population in United States. To advance the knowledge in pathology, our study investigates into the common inflammatory feature in CD across different inflammation statuses by single-cell transcriptomics. First, we provided a detailed mucosal cellular landscape of terminal ileum (TI) and ascending colon (AC), with endoscopic diagnosis (CD inflamed, adjacent-to-inflamed, non-inflamed and non-IBD control), including a cohort of patients undergoing biological treatments. Differences between regions (TI and AC), and features of mucosal inflammation status in cellular composition are captured within the cellular landscapes. Second, we identified an inflammation cascade that include follicle-associated enterocytes and macrophages via molecules like CCL20 and S100As, as key mediators of CD inflammation. These key mediators serve as hubs in imputed cell-cell interactions under CD inflammation, expanding the interplay network with increasing disease severity. Finally, we demonstrate a scoring method by surveying the mucosa, using GWAS loci, and transcriptome features including differentially expressed genes (DEGs), and genes from a novel singular value decomposition (SVD)-based co-expression network analysis framework. Applying independently to the epithelial and immune lineage, we identify inflammation signatures that reflect disease severity. Furthermore, we report a short, robust list of epithelial and immune transcript makers whose expressions harmonize with endoscopic diagnosis and histological assessment. These markers are merely within known IBD GWAS loci. Collectively, this study narrates a shared inflammation pattern involving cells and cytokines for active CD and present a short list of markers for metrical inflammation assessment.