Department of Pediatric Surgery, University Medical Center Mannheim, University Heidelberg, Mannheim, Germany.
Front Immunol. 2024 Jul 22;15:1434281. doi: 10.3389/fimmu.2024.1434281. eCollection 2024.
Necrotizing enterocolitis (NEC) is one of the most devasting diseases affecting preterm neonates. However, despite a lot of research, NEC's pathogenesis remains unclear. It is known that the pathogenesis is a multifactorial process, including (1) a pathological microbiome with abnormal bacterial colonization, (2) an immature immune system, (3) enteral feeding, (3) an impairment of microcirculation, and (4) possibly ischemia-reperfusion damage to the intestine. Overall, the immaturity of the mucosal barrier and the increased expression of Toll-like receptor 4 (TLR4) within the intestinal epithelium result in an intestinal hyperinflammation reaction. Concurrently, a deficiency in counter-regulatory mediators can be seen. The sum of these processes can ultimately result in intestinal necrosis leading to very high mortality rates of the affected neonates. In the last decade no substantial advances in the treatment of NEC have been made. Thus, NEC animal models as well as models have been employed to better understand NEC's pathogenesis on a cellular and molecular level. This review will highlight the different models currently in use to study immunological aspects of NEC.
坏死性小肠结肠炎(NEC)是影响早产儿的最具破坏性疾病之一。然而,尽管进行了大量研究,NEC 的发病机制仍不清楚。已知发病机制是一个多因素的过程,包括(1)病理性微生物组,伴有异常细菌定植,(2)不成熟的免疫系统,(3)肠内喂养,(3)微循环受损,以及(4)肠道可能发生缺血再灌注损伤。总的来说,肠黏膜屏障的不成熟和肠上皮内 Toll 样受体 4(TLR4)的过度表达导致肠道过度炎症反应。同时,可以看到对抗调节介质的缺乏。这些过程的总和最终可能导致肠道坏死,导致受影响的新生儿死亡率非常高。在过去的十年中,NEC 的治疗没有取得实质性进展。因此,人们使用 NEC 动物模型和细胞模型来更好地理解 NEC 在细胞和分子水平上的发病机制。这篇综述将重点介绍目前用于研究 NEC 免疫学方面的不同模型。