Bamias Giorgos, Cominelli Fabio
aAcademic Department of Gastroenterology, Kapodistrian University of Athens, Laikon Hospital, Athens, Greece bDivision of Gastrointestinal and Liver Disease, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USA.
Curr Opin Gastroenterol. 2016 Nov;32(6):437-442. doi: 10.1097/MOG.0000000000000315.
Cytokines of the intestinal microenvironment largely dictate immunological responses after mucosal insults and the dominance of homeostatic or proinflammatory pathways. This review presents important recent studies on the role of specific cytokines in the pathogenesis of intestinal inflammation.
The particular mucosal effects of cytokines depend on their inherent properties but also the cellular origin, type of stimulatory antigens, intermolecular interactions, and the particular immunological milieu. Novel cytokines of the interleukin-1 (IL-1) family, including IL-33 and IL-36, have dominant roles in mucosal immunity, whereas more established ones such as IL-18 are constantly enriched with unique properties. Th17 cells are important mucosal constituents, although their profound plasticity, makes the specific set of cytokines they secrete more important than their mere numbers. Finally, various cytokines, such as tumor necrosis factor-α, IL-6, tumor necrosis factor-like cytokine 1A, and death receptor, 3 demonstrate dichotomous roles with mucosa-protective function in acute injury but proinflammatory effects during chronic inflammation.
The role of cytokines in mucosal health and disease is increasingly revealed. Such information not only will advance our understanding of the pathogenesis of gut inflammation, but also set the background for development of reliable diagnostic and prognostic biomarkers and cytokine-specific therapies.
肠道微环境中的细胞因子在很大程度上决定了黏膜损伤后的免疫反应以及稳态或促炎途径的主导地位。本综述介绍了近期关于特定细胞因子在肠道炎症发病机制中作用的重要研究。
细胞因子的特定黏膜效应不仅取决于其固有特性,还取决于细胞来源、刺激性抗原类型、分子间相互作用以及特定的免疫环境。白细胞介素-1(IL-1)家族的新型细胞因子,包括IL-33和IL-36,在黏膜免疫中起主导作用,而诸如IL-18等更为成熟的细胞因子则不断展现出独特特性。Th17细胞是重要的黏膜成分,尽管其具有高度可塑性,但其分泌的特定细胞因子组合比其数量更为重要。最后,多种细胞因子,如肿瘤坏死因子-α、IL-6、肿瘤坏死因子样细胞因子1A和死亡受体3,在急性损伤中具有黏膜保护功能,但在慢性炎症中具有促炎作用,表现出双重作用。
细胞因子在黏膜健康和疾病中的作用日益明晰。此类信息不仅将增进我们对肠道炎症发病机制的理解,还为开发可靠的诊断和预后生物标志物以及细胞因子特异性疗法奠定基础。