Mucosal Profiling of Pediatric-Onset Colitis and IBD Reveals Common Pathogenics and Therapeutic Pathways.
Pediatric-onset colitis and inflammatory bowel disease (IBD) have significant effects on the growth of infants and children, but the etiopathogenesis underlying disease subtypes remains incompletely understood. Here, we report single-cell clustering, immune phenotyping, and risk gene analysis for children with undifferentiated colitis, Crohn's disease, and ulcerative colitis. We demonstrate disease-specific characteristics, as well as common pathogenesis marked by impaired cyclic AMP (cAMP)-response signaling. Specifically, infiltration of PDE4B- and TNF-expressing macrophages, decreased abundance of CD39-expressing intraepithelial T cells, and platelet aggregation and release of 5-hydroxytryptamine at the colonic mucosae were common in colitis and IBD patients. Targeting these pathways by using the phosphodiesterase inhibitor dipyridamole restored immune homeostasis and improved colitis symptoms in a pilot study. In summary, comprehensive analysis of the colonic mucosae has uncovered common pathogenesis and therapeutic targets for children with colitis and IBD.
Antigens, CD; Apyrase; B-Lymphocytes; Cell Death; Cellular Microenvironment; Child; Cohort Studies; Colon; Dendritic Cells; Dipyridamole; Endothelial Cells; Epithelial Cells; Fibroblasts; Gene Expression Regulation; Genetic Predisposition to Disease; Homeostasis; Humans; Immunoglobulin G; Immunologic Memory; Inflammation; Inflammatory Bowel Diseases; Interferon Type I; Intestinal Mucosa; Macrophages; Methylprednisolone; Myeloid Cells
CASP7; CD39; PDE4B; TNF; cAMP; dipyridamole; pediatric-onset colitis and IBD; platelet; risk genes; single-cell RNA expression
Huang B, Chen Z, Geng L, et al. Mucosal Profiling of Pediatric-Onset Colitis and IBD Reveals Common Pathogenics and Therapeutic Pathways. Cell. 2019;179(5):1160-1176.e24. doi:10.1016/j.cell.2019.10.027