O'Shea Kelly M, Aceves Seema S, Dellon Evan S, Gupta Sandeep K, Spergel Jonathan M, Furuta Glenn T, Rothenberg Marc E
Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Division of Allergy Immunology, Center for Immunity, Infection and Inflammation, University of California San Diego and Rady Children's Hospital San Diego, California.
Gastroenterology. 2018 Jan;154(2):333-345. doi: 10.1053/j.gastro.2017.06.065. Epub 2017 Jul 27.
Eosinophilic esophagitis is an emerging disease that is distinguished from gastroesophageal reflux disease by the expression of a unique esophageal transcriptome and the interplay of early life environmental factors with distinct genetic susceptibility elements at 5q22 (TSLP) and 2p23 (CAPN14). Rare genetic syndromes have uncovered the contribution of barrier disruption, mediated in part by defective desmosomes and dysregulated transforming growth factor beta production and signaling, to eosinophilic esophagitis pathophysiology. Experimental modeling has defined a cooperative role of activated eosinophils, mast cells, and the cytokines IL-5 and IL-13, mediated by allergic sensitization to multiple foods. Understanding these processes is opening the way to better treatment based on disrupting allergic inflammatory and type 2 cytokine-mediated responses, including anti-cytokine therapeutics and dietary therapy.
嗜酸性粒细胞性食管炎是一种新出现的疾病,它通过独特的食管转录组表达以及早期生活环境因素与5q22(TSLP)和2p23(CAPN14)处不同遗传易感性元件之间的相互作用,与胃食管反流病相区分。罕见的遗传综合征揭示了屏障破坏在嗜酸性粒细胞性食管炎病理生理学中的作用,这种破坏部分由桥粒缺陷以及转化生长因子β产生和信号传导失调介导。实验模型已经确定了活化的嗜酸性粒细胞、肥大细胞以及细胞因子IL-5和IL-13的协同作用,这种作用由对多种食物的过敏致敏介导。了解这些过程正在为基于破坏过敏性炎症和2型细胞因子介导的反应的更好治疗开辟道路,包括抗细胞因子治疗和饮食治疗。