| Literature DB >> 31730855 |
Bing Huang1, Zhanghua Chen2, Lanlan Geng1, Jun Wang1, Huiying Liang1, Yujie Cao3, Huan Chen1, Wanming Huang1, Meiling Su1, Hanqing Wang1, Yanhui Xu1, Yukun Liu1, Bingtai Lu1, Huifang Xian1, Huiwen Li1, Huilin Li1, Lu Ren1, Jing Xie1, Liping Ye1, Hongli Wang1, Junhong Zhao1, Peiyu Chen1, Li Zhang1, Shanmeizi Zhao1, Ting Zhang4, Banglao Xu4, Di Che1, Wenyue Si1, Xiaoqiong Gu1, Liang Zeng1, Yong Wang1, Dingyou Li5, Yifan Zhan6, David Delfouneso1, Andrew M Lew6, Jun Cui7, Wai Ho Tang1, Yan Zhang1, Sitang Gong8, Fan Bai9, Min Yang10, Yuxia Zhang11.
Abstract
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.Entities:
Keywords: CASP7; CD39; PDE4B; TNF; cAMP; dipyridamole; pediatric-onset colitis and IBD; platelet; risk genes; single-cell RNA expression
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Year: 2019 PMID： 31730855 DOI： 10.1016/j.cell.2019.10.027
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582