Bamias Giorgos, Arseneau Kristen O, 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. 2014 Nov;30(6):547-52. doi: 10.1097/MOG.0000000000000118.
Cytokines are integral mediators for maintaining intestinal mucosal homeostasis, as well as prominent effector molecules during chronic gut inflammatory diseases. This review focuses on recent studies of the role of specific cytokines in mucosal immunity.
Dichotomous, or even opposing, functions have been described for several cytokines involved in intestinal innate immunity (most notably for members of the interleukin-1 family), which depend on the specific inflammatory conditions within the intestinal mucosa. For example, both interleukin-1α and interleukin-33 exhibit 'alarmin'-type properties that can signal tissue or cell damage, which further add to their well described proinflammatory roles. Costimulatory molecules of the tumor necrosis factor/tumor necrosis factor receptor superfamily, such as TNF-like cytokine 1A and LIGHT, are actively involved in mucosal proinflammatory pathways, but also may exert protection against infectious agents to facilitate recovery from acute inflammation. Finally, innate lymphoid cells are increasingly recognized as important cellular sources of pivotal mucosal cytokines, including the interleukin-23/T helper 17 cytokine, interleukin-22.
Elucidating the complexity of cytokine signaling within the normal mucosa and during acute and chronic inflammation will be a pivotal step toward understanding the pathogenesis of immune-mediated gut diseases and developing effective therapies to treat them.
细胞因子是维持肠道黏膜稳态的重要介质，也是慢性肠道炎症性疾病中的重要效应分子。本综述聚焦于特定细胞因子在黏膜免疫中作用的近期研究。
参与肠道固有免疫的几种细胞因子（最显著的是白细胞介素-1家族成员）具有二分甚至相反的功能，这取决于肠道黏膜内的特定炎症状况。例如，白细胞介素-1α和白细胞介素-33都具有“警报素”样特性，可发出组织或细胞损伤信号，这进一步增加了它们广为人知的促炎作用。肿瘤坏死因子/肿瘤坏死因子受体超家族的共刺激分子，如肿瘤坏死因子样细胞因子1A和LIGHT，积极参与黏膜促炎途径，但也可能对感染因子发挥保护作用，以促进从急性炎症中恢复。最后，固有淋巴细胞越来越被认为是关键黏膜细胞因子的重要细胞来源，包括白细胞介素-23/辅助性T细胞17细胞因子、白细胞介素-22。
阐明正常黏膜以及急性和慢性炎症期间细胞因子信号传导的复杂性，将是理解免疫介导的肠道疾病发病机制并开发有效治疗方法的关键一步。
