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Mucosal Profiling of Pediatric-Onset Colitis and IBD Reveals Common Pathogenics and Therapeutic Pathways.
Cell ( IF 45.5 ) Pub Date : 2019-11-14 , DOI: 10.1016/j.cell.2019.10.027 Bing Huang 1 , Zhanghua Chen 2 , Lanlan Geng 1 , Jun Wang 1 , Huiying Liang 1 , Yujie Cao 3 , Huan Chen 1 , Wanming Huang 1 , Meiling Su 1 , Hanqing Wang 1 , Yanhui Xu 1 , Yukun Liu 1 , Bingtai Lu 1 , Huifang Xian 1 , Huiwen Li 1 , Huilin Li 1 , Lu Ren 1 , Jing Xie 1 , Liping Ye 1 , Hongli Wang 1 , Junhong Zhao 1 , Peiyu Chen 1 , Li Zhang 1 , Shanmeizi Zhao 1 , Ting Zhang 4 , Banglao Xu 4 , Di Che 1 , Wenyue Si 1 , Xiaoqiong Gu 1 , Liang Zeng 1 , Yong Wang 1 , Dingyou Li 5 , Yifan Zhan 6 , David Delfouneso 1 , Andrew M Lew 6 , Jun Cui 7 , Wai Ho Tang 1 , Yan Zhang 1 , Sitang Gong 1 , Fan Bai 8 , Min Yang 1 , Yuxia Zhang 9
Cell ( IF 45.5 ) Pub Date : 2019-11-14 , DOI: 10.1016/j.cell.2019.10.027 Bing Huang 1 , Zhanghua Chen 2 , Lanlan Geng 1 , Jun Wang 1 , Huiying Liang 1 , Yujie Cao 3 , Huan Chen 1 , Wanming Huang 1 , Meiling Su 1 , Hanqing Wang 1 , Yanhui Xu 1 , Yukun Liu 1 , Bingtai Lu 1 , Huifang Xian 1 , Huiwen Li 1 , Huilin Li 1 , Lu Ren 1 , Jing Xie 1 , Liping Ye 1 , Hongli Wang 1 , Junhong Zhao 1 , Peiyu Chen 1 , Li Zhang 1 , Shanmeizi Zhao 1 , Ting Zhang 4 , Banglao Xu 4 , Di Che 1 , Wenyue Si 1 , Xiaoqiong Gu 1 , Liang Zeng 1 , Yong Wang 1 , Dingyou Li 5 , Yifan Zhan 6 , David Delfouneso 1 , Andrew M Lew 6 , Jun Cui 7 , Wai Ho Tang 1 , Yan Zhang 1 , Sitang Gong 1 , Fan Bai 8 , Min Yang 1 , Yuxia Zhang 9
Affiliation
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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.
中文翻译：
小儿发作性结肠炎和IBD的粘膜分析揭示了常见的病因和治疗途径。
小儿发作性结肠炎和炎性肠病（IBD）对婴儿和儿童的生长有显著作用，但对疾病亚型的病因病因尚不完全了解。在这里，我们报告了未分化结肠炎，克罗恩病和溃疡性结肠炎患儿的单细胞聚类，免疫表型分析和风险基因分析。我们表现出特定于疾病的特征，以及以受损的循环AMP（cAMP）反应信号为标志的常见发病机理。具体而言，在结肠炎和IBD患者中，常见的是表达PDE4B和TNF的巨噬细胞浸润，表达CD39的上皮内T细胞减少，结肠黏膜血小板聚集和5-羟色胺释放。在一项先导研究中，通过使用磷酸二酯酶抑制剂双嘧达莫来靶向这些途径可恢复免疫稳态并改善结肠炎症状。总而言之，对结肠粘膜的全面分析发现了结肠炎和IBD儿童的常见发病机制和治疗目标。
更新日期：2019-11-14
中文翻译：
小儿发作性结肠炎和IBD的粘膜分析揭示了常见的病因和治疗途径。
小儿发作性结肠炎和炎性肠病（IBD）对婴儿和儿童的生长有显著作用，但对疾病亚型的病因病因尚不完全了解。在这里，我们报告了未分化结肠炎，克罗恩病和溃疡性结肠炎患儿的单细胞聚类，免疫表型分析和风险基因分析。我们表现出特定于疾病的特征，以及以受损的循环AMP（cAMP）反应信号为标志的常见发病机理。具体而言，在结肠炎和IBD患者中，常见的是表达PDE4B和TNF的巨噬细胞浸润，表达CD39的上皮内T细胞减少，结肠黏膜血小板聚集和5-羟色胺释放。在一项先导研究中，通过使用磷酸二酯酶抑制剂双嘧达莫来靶向这些途径可恢复免疫稳态并改善结肠炎症状。总而言之，对结肠粘膜的全面分析发现了结肠炎和IBD儿童的常见发病机制和治疗目标。
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