Mucosal profiling of pediatric-onset colitis and IBD reveals common pathogenics and therapeutic pathways

Huang, B; Chen, Z; Geng, L; Wang, J; Liang, H; Cao, Y; Chen, H; Huang, W; Su, M; Wang, H; Xu, Y; Liu, Y; Lu, B; Xian, H; Li, H; Ren, L; Xie, J; Ye, L; Zhao, J; Chen, P; Zhang, L; Zhao, S; Zhang, T; Xu, B; Che, D; Si, W; Gu, X; Zeng, L; Wang, Y; Li, D; Zhan, Y; Delfouneso, D; Lew, AM; Cui, J; Tang, WH; Zhang, Y; Gong, S; Bai, F; Yang, M

Author(s): Huang, B; Chen, Z; Geng, L; Wang, J; Liang, H; Cao, Y; Chen, H; Huang, W; Su, M; Wang, H; Xu, Y; Liu, Y; Lu, B; Xian, H; Li, H; Ren, L; Xie, J; Ye, L; Zhao, J; Chen, P; Zhang, L; Zhao, S; Zhang, T; Xu, B; Che, D; Si, W; Gu, X; Zeng, L; Wang, Y; Li, D; Zhan, Y; Delfouneso, D; Lew, AM; Cui, J; Tang, WH; Zhang, Y; Gong, S; Bai, F; Yang, M;
Details: Publication Year 2019-11-14,Volume 179,Issue #5,Page 1160-1176 e24
Journal Title: Cell
Publication Type: Journal Article
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.
Publisher: Cell Press
Research Division(s): Immunology
PubMed ID: 31730855
Publisher's Version: https://doi.org/10.1016/j.cell.2019.10.027
NHMRC Grants: NHMRC/1037321, NHMRC/1105209, NHMRC/1143976, NHMRC/108032,
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2019-11-20 02:45:21

Last Modified: 2019-11-21 09:56:23