Intestinal epithelium, intraepithelial lymphocytes and the gut microbiota-Key players in the pathogenesis of celiac disease

作     者：Bozena Cukrowska Agnieszka Sowińska Joanna Beata Bierla Elzbieta Czarnowska Anna Rybak Urszula Grzybowska-Chlebowczyk 

作者机构：Department of PathologyThe Children's Memorial Health Institute Department of GastroenterologyDivision of Neurogastroenterology and MotilityGreat Ormond Street Hospital Department of PediatricsSchool of MedicineMedical University of Silesia 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2017年第23卷第42期

页      面：7505-7518页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：Supported by the Children’s Memorial Health Institute Grants No.236/15 No.243/16 and No.S147/2016 

主　　题：Celiac disease Intestinal microbiota Epithelium Intraepithelial lymphocytes Intestinal barrier 

摘      要：Celiac disease(CD) is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals. Before activating the immune system, gluten peptides are transferred by the epithelial barrier to the mucosal lamina propria, where they are deamidated by intestinal tissue transglutaminase 2. As a result, they strongly bind to human leucocyte antigens(HLAs), especially HLA-DQ2 and HLA-DQ8, expressed on antigen-presenting cells. This induces an inflammatory response, which results in small bowel enteropathy. Although gluten is the main external trigger activating both innate and adaptive(specific) immunity, its presence in the intestinal lumen does not fully explain CD pathogenesis. It has been hypothesized that an early disruption of the gut barrier in genetically susceptible individuals, which would result in an increased intestinal permeability, could precede the onset of gluten-induced immune events. The intestinal barrier is a complex functional structure, whose functioning is dependent on intestinal microbiotahomeostasis, epithelial layer integrity, and the gutassociated lymphoid tissue with its intraepithelial lymphocytes(IELs). The aim of this paper was to review the current literature and summarize the role of the gut microbiota, epithelial cells and their intercellular junctions, and IELs in CD development.