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

被引：216

作者：

Huang, Bing ^{[1
]}

Chen, Zhanghua ^{[2
]}

Geng, Lanlan ^{[1
]}

Wang, Jun ^{[1
]}

Liang, Huiying ^{[1
]}

Cao, Yujie ^{[3
]}

Chen, Huan ^{[1
]}

Huang, Wanming ^{[1
]}

Su, Meiling ^{[1
]}

Wang, Hanqing ^{[1
]}

Xu, Yanhui ^{[1
]}

Liu, Yukun ^{[1
]}

Lu, Bingtai ^{[1
]}

Xian, Huifang ^{[1
]}

Li, Huiwen ^{[1
]}

Li, Huilin ^{[1
]}

Ren, Lu ^{[1
]}

Xie, Jing ^{[1
]}

Ye, Liping ^{[1
]}

Wang, Hongli ^{[1
]}

Zhao, Junhong ^{[1
]}

Chen, Peiyu ^{[1
]}

Zhang, Li ^{[1
]}

Zhao, Shanmeizi ^{[1
]}

Zhang, Ting ^{[4
]}

Xu, Banglao ^{[4
]}

Che, Di ^{[1
]}

Si, Wenyue ^{[1
]}

Gu, Xiaoqiong ^{[1
]}

Zeng, Liang ^{[1
]}

Wang, Yong ^{[1
]}

Li, Dingyou ^{[5
]}

Zhan, Yifan ^{[6
,7
]}

Delfouneso, David ^{[1
]}

Lew, Andrew M. ^{[6
,7
]}

Cui, Jun ^{[8
]}

Tang, Wai Ho ^{[1
]}

Zhang, Yan ^{[1
]}

Gong, Sitang ^{[1
]}

Bai, Fan ^{[2
,9
]}

Yang, Min ^{[1
]}

Zhang, Yuxia ^{[1
,10
]}

机构：

[1] Guangzhou Med Univ, Guangzhou Inst Pediat, Guangzhou Women & Childrens Med Ctr, Dept Gastroenterol, Guangzhou 510623, Guangdong, Peoples R China

[2] Peking Univ, Sch Life Sci, Biomed Pioneering Innovat Ctr BIOPIC, Beijing 100871, Peoples R China

[3] Univ Hong Kong, Dept Pediat & Adolescent Med, LKS Fac Med, Pokfulam, Hong Kong, Peoples R China

[4] South China Univ Technol, Dept Lab Med, Guangzhou Peoples Hosp 1, Sch Med, Guangzhou 510180, Guangdong, Peoples R China

[5] Univ Missouri, Childrens Mercy Hosp, Div Gastroenterol, Sch Med, Kansas City, MO 64108 USA

[6] Univ Melbourne, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia

[7] Univ Melbourne, Dept Med Biol, Parkville, Vic 3052, Australia

[8] Sun Yat Sen Univ, Sch Life Sci, Guangzhou 510006, Guangdong, Peoples R China

[9] Peking Univ, Ctr Translat Canc Res, Hosp 1, Beijing 100871, Peoples R China

[10] Zhengzhou Univ, Affiliated Hosp 3, Zhengzhou 450052, Henan, Peoples R China

来源：

CELL | 2019年 / 179卷 / 05期

基金：

英国医学研究理事会; 中国博士后科学基金; 中国国家自然科学基金;

关键词：

INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; ULCERATIVE-COLITIS; DENDRITIC CELLS; PLASMA-CELLS; CD39; ACTIVATION; EXPRESSION; MIGRATION; SEVERITY;

D O I：

10.1016/j.cell.2019.10.027

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1160 / +

页数：41

共 83 条

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