广州医科大学张玉霞、杨敏、龚四堂等与北京大学白凡等研究人员合作，通过综合评估儿童结肠炎或炎症性肠病揭示了其致病机制和治疗方法。相关论文于2019年11月14日发表在《细胞》杂志上。
人肠粘膜由单层上皮细胞以及上皮内基质和免疫细胞组成。完整的上皮屏障可防止未消化的食物蛋白、微生物和病原体激活免疫细胞。IBD是克罗恩病（CD）和溃疡性结肠炎（UC）的专业术语。根据欧洲儿科胃肠病学肝病和营养学会（ESPGHAN）修订的标准，尽管小儿发作性结肠炎通常表现出非经典的CD或UC表型，但他们也被归类为小儿IBD（PIBD）。然而，小儿发作性结肠炎是否是IBD的危险因素，以及这些疾病是否具有共同的发病机制仍未得到回答。近几十年来，全世界报道的PIBD发病率有所上升。这种增加是由与现代环境相关的变化驱动的，这对携带IBD风险基因的个体产生了深远的不利影响。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影响，但对疾病亚型的病因病因尚不完全了解。
研究人员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。研究人员揭示了特定于疾病的特征，以及由受损的循环AMP（cAMP）反应信号标记的常见发病机理。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。
附：英文原文
Title: Mucosal Profiling of Pediatric-Onset Colitis and IBD Reveals Common Pathogenics and Therapeutic Pathways
Author: 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, Junhong Zhao, Peiyu Chen, Li Zhang, Shanmeizi Zhao, Ting Zhang, Banglao Xu, Di Che, Wenyue Si, Xiaoqiong Gu, Liang Zeng, Yong Wang, Dingyou Li, Yifan Zhan, David Delfouneso, Andrew M. Lew, Jun Cui, Wai Ho Tang, Yan Zhang, Sitang Gong, Fan Bai, Min Yang, Yuxia Zhang
Issue&Volume: 2019/11/14
Abstract: Pediatric-onset colitis and inflammatory bowel disease (IBD) have significant effectson the growth of infants and children, but the etiopathogenesis underlying diseasesubtypes 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 mucosaewere common in colitis and IBD patients. Targeting these pathways by using the phosphodiesteraseinhibitor dipyridamole restored immune homeostasis and improved colitis symptoms ina pilot study. In summary, comprehensive analysis of the colonic mucosae has uncoveredcommon pathogenesis and therapeutic targets for children with colitis and IBD.
DOI: 10.1016/j.cell.2019.10.027
Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31177-8