Hodzic Zerina, Bolock Alexa M, Good Misty
University of Pittsburgh School of Medicine , Pittsburgh, PA , USA.
Division of Newborn Medicine, Department of Pediatrics, Washington University School of Medicine , St. Louis, MO , USA.
Front Pediatr. 2017 Mar 3;5:40. doi: 10.3389/fped.2017.00040. eCollection 2017.
Necrotizing enterocolitis (NEC) is the most devastating gastrointestinal disease of prematurity. Although the precise cause is not well understood, the main risk factors thought to contribute to NEC include prematurity, formula feeding, and bacterial colonization. Recent evidence suggests that NEC develops as a consequence of intestinal hyper-responsiveness to microbial ligands upon bacterial colonization in the preterm infant, initiating a cascade of aberrant signaling events, and a robust pro-inflammatory mucosal immune response. We now have a greater understanding of important mechanisms of disease pathogenesis, such as the role of cytokines, immunoglobulins, and immune cells in NEC. In this review, we will provide an overview of the mucosal immunity of the intestine and the relationship between components of the mucosal immune system involved in the pathogenesis of NEC, while highlighting recent advances in the field that have promise as potential therapeutic targets. First, we will describe the cellular components of the intestinal epithelium and mucosal immune system and their relationship to NEC. We will then discuss the relationship between the gut microbiota and cell signaling that underpins disease pathogenesis. We will conclude our discussion by highlighting notable therapeutic advancements in NEC that target the intestinal mucosal immunity.
坏死性小肠结肠炎(NEC)是最具破坏性的早产儿胃肠道疾病。尽管确切病因尚不完全清楚,但被认为导致NEC的主要危险因素包括早产、配方奶喂养和细菌定植。最近的证据表明,NEC是由于早产儿细菌定植后肠道对微生物配体的高反应性而发展的,引发了一系列异常信号事件以及强烈的促炎性黏膜免疫反应。我们现在对疾病发病机制的重要机制有了更深入的了解,例如细胞因子、免疫球蛋白和免疫细胞在NEC中的作用。在这篇综述中,我们将概述肠道黏膜免疫以及参与NEC发病机制的黏膜免疫系统各组成部分之间的关系,同时强调该领域有望成为潜在治疗靶点的最新进展。首先,我们将描述肠道上皮和黏膜免疫系统的细胞组成部分及其与NEC的关系。然后,我们将讨论肠道微生物群与支撑疾病发病机制的细胞信号传导之间的关系。我们将通过强调针对肠道黏膜免疫的NEC显著治疗进展来结束我们的讨论。