Mucosal Profiling of Pediatric-Onset Colitis and IBD Reveals Common Pathogenics and Therapeutic Pathways

Publication date: 14 November 2019Source: Cell, Volume 179, Issue 5Author(s): Bing Huang, Zhanghua Chen, Lanlan Geng, Jun Wang, Huiying Liang, Yujie Cao, Huan Chen, Wanming Huang, Meiling Su, Hanqing Wang, Yanhui Xu, Yukun Liu, Bingtai Lu, Huifang Xian, Huiwen Li, Huilin Li, Lu Ren, Jing Xie, Liping Ye, Hongli WangSummaryPediatric-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.Graphical Abstract
Source: Cell - Category: Cytology Source Type: research