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, LuRen, Jing Xie, Liping Ye, Hongli Wang, Junhong Zhao, Peiyu Chen, Li Zhang, Shanmeizi Zhao, Ting Zhang, Banglao Xu, Di Che, Wenyue Si, Xiaoqiong Gu, Liang Zeng, Yong Wang, Dingyou Li, Yifan Zhan, David Delfouneso, Andrew M.Lew, Jun Cui, Wai Ho Tang, Yan Zhang, Sitang Gong, Fan Bai, Min Yang, Yuxia Zhang
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.