Department of Medicine 1, Friedrich-Alexander-University Erlangen-Nuremberg, 91052 Erlangen, Germany.
Cells. 2021 Jan 9;10(1):111. doi: 10.3390/cells10010111.
Cytokines are small proteins that are secreted by a vast majority of cell types in the gut. They not only establish cell-to-cell interactions and facilitate cellular signaling, but also regulate both innate and adaptive immune responses, thereby playing a central role in genetic, inflammatory, and infectious diseases of the gut. Both, immune cells and gut epithelial cells, play important roles in intestinal disease development. The epithelium is located in between the mucosal immune system and the gut microbiome. It not only establishes an efficient barrier against gut microbes, but it also signals information from the gut lumen and its composition to the immune cell compartment. Communication across the epithelial cell layer also occurs in the other direction. Intestinal epithelial cells respond to immune cell cytokines and their response influences and shapes the microbial community within the gut lumen. Thus, the epithelium should be seen as a translator or a moderator between the microbiota and the mucosal immune system. Proper communication across the epithelium seems to be a key to gut homeostasis. Indeed, current genome-wide association studies for intestinal disorders have identified several disease susceptibility loci, which map cytokine signatures and their related signaling genes. A thorough understanding of this tightly regulated cytokine signaling network is crucial. The main objective of this review was to shed light on how cytokines can orchestrate epithelial functions such as proliferation, cell death, permeability, microbe interaction, and barrier maintenance, thereby safeguarding host health. In addition, cytokine-mediated therapy for inflammation and cancer are discussed.
细胞因子是由肠道中绝大多数细胞类型分泌的小蛋白。它们不仅建立细胞间相互作用并促进细胞信号转导，而且还调节固有和适应性免疫反应，从而在肠道的遗传、炎症和感染性疾病中发挥核心作用。免疫细胞和肠道上皮细胞都在肠道疾病的发展中起着重要作用。上皮细胞位于黏膜免疫系统和肠道微生物群之间。它不仅建立了对肠道微生物的有效屏障，而且还将来自肠道腔及其成分的信息传递给免疫细胞区室。上皮细胞层之间也会发生相反方向的通讯。肠道上皮细胞对免疫细胞细胞因子做出反应，其反应会影响和塑造肠道腔中的微生物群落。因此，上皮细胞应该被视为微生物群和黏膜免疫系统之间的翻译者或调节剂。上皮细胞之间的适当通讯似乎是肠道稳态的关键。事实上，目前针对肠道疾病的全基因组关联研究已经确定了几个疾病易感性位点，这些位点映射了细胞因子特征及其相关信号基因。深入了解这个受严格调控的细胞因子信号网络至关重要。本综述的主要目的是阐明细胞因子如何协调上皮细胞的功能，如增殖、细胞死亡、通透性、微生物相互作用和屏障维持，从而保障宿主健康。此外，还讨论了细胞因子介导的炎症和癌症治疗。
