Journal article

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

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 Wang Show all

CELL | CELL PRESS | Published : 2019

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-hydroxytr..

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Grants

Awarded by National Natural Science Foundation of China


Awarded by National Key Research and Development Program


Awarded by National Science and Technology Major Project


Awarded by Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease


Awarded by China Postdoctoral Science Foundation


Awarded by Guangzhou Women and Children's Medical Center Fund


Awarded by National Health and Medical Research Council of Australia


Funding Acknowledgements

The National Natural Science Foundation of China (91742109, 31770978, 31722003, 31770925, 31370847, and 81770552), the National Key Research and Development Program (2016YFC0900102), the National Science and Technology Major Project (2018ZX10302205), the Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease (2019B030301004), the China Postdoctoral Science Foundation (2017M622656), the Guangzhou Women and Children's Medical Center Fund (5001-3001032, Pre-NSFC-2016-004, and 5001-3001068) and the National Health and Medical Research Council of Australia (1037321, 1105209, 1143976, and 1080321, to A.L.) funded this study. We thank patients and their guardians, the Clinical Biological Resource Bank, and the National Supercomputer Center in Guangzhou at Sun Yat-Sen University for support of the study.