Mucosal Profiling of Pediatric-Onset Colitis and IBD Reveals Common Pathogenics and Therapeutic Pathways
| Autor: | Lu Ren, Yifan Zhan, Huilin Li, Zhang Ting, Yan Zhang, Di Che, Junhong Zhao, Yukun Liu, Min Yang, Yong Wang, Xiaoqiong Gu, Wai Ho Tang, Liping Ye, Hanqing Wang, David Delfouneso, Ding-You Li, Hongli Wang, Li Zhang, Sitang Gong, Huiying Liang, Yuxia Zhang, Shanmeizi Zhao, Liang Zeng, Jing Xie, Wanming Huang, Yanhui Xu, Wenyue Si, Huan Chen, Zhanghua Chen, Jun Wang, Peiyu Chen, Bingtai Lu, Lanlan Geng, Jun Cui, Yujie Cao, Meiling Su, Huifang Xian, Bing Huang, Banglao Xu, Huiwen Li, Andrew M. Lew, Fan Bai |
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| Rok vydání: | 2019 |
| Předmět: |
Colon
Inflammation Biology Methylprednisolone Inflammatory bowel disease General Biochemistry Genetics and Molecular Biology Cohort Studies Pathogenesis 03 medical and health sciences 0302 clinical medicine PDE4B Immune system Intestinal mucosa Antigens CD medicine Homeostasis Humans Genetic Predisposition to Disease Myeloid Cells Intestinal Mucosa Colitis Child 030304 developmental biology B-Lymphocytes 0303 health sciences Cell Death Macrophages Apyrase Endothelial Cells Epithelial Cells Dendritic Cells Dipyridamole Fibroblasts Inflammatory Bowel Diseases medicine.disease Ulcerative colitis digestive system diseases Cellular Microenvironment Gene Expression Regulation Immunoglobulin G Interferon Type I Immunology medicine.symptom Immunologic Memory 030217 neurology & neurosurgery |
| Zdroj: | Cell. 179:1160-1176.e24 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2019.10.027 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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