Department of Medicine 1, University of Erlangen-Nuremberg, Kussmaul Campus for Medical Research and Translational Research Center, 91054 Erlangen, Germany.
Vaccines (Basel). 2016 Feb 29;4(1):5. doi: 10.3390/vaccines4010005.
Cytokines are believed to be crucial mediators of chronic intestinal inflammation in inflammatory bowel diseases (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC). Many of these cytokines trigger cellular effects and functions through signaling via janus kinase (JAK) and signal transducer and activator of transcription (STAT) molecules. In this way, JAK/STAT signaling controls important events like cell differentiation, secretion of cytokines or proliferation and apoptosis in IBD in both adaptive and innate immune cells. Moreover, JAK/STAT signaling, especially via the IL-6/STAT3 axis, is believed to be involved in the transition of inflammatory lesions to tumors leading to colitis-associated cancer (CAC). In this review, we will introduce the main cellular players and cytokines that contribute to pathogenesis of IBD by JAK/STAT signaling, and will highlight the integrative function that JAK/STATs exert in this context as well as their divergent role in different cells and processes. Moreover, we will explain current concepts of the implication of JAK/STAT signaling in CAC and finally discuss present and future therapies for IBD that interfere with JAK/STAT signaling.
细胞因子被认为是炎症性肠病（IBD）中慢性肠道炎症的关键介质，如克罗恩病（CD）和溃疡性结肠炎（UC）。这些细胞因子中的许多通过 Janus 激酶（JAK）和信号转导和转录激活因子（STAT）分子的信号转导触发细胞效应和功能。通过这种方式，JAK/STAT 信号转导控制着 IBD 中适应性和固有免疫细胞中重要的事件，如细胞分化、细胞因子分泌或增殖和凋亡。此外，JAK/STAT 信号转导，特别是通过 IL-6/STAT3 轴，被认为参与炎症病变向肿瘤的转化，导致结肠炎相关癌症（CAC）。在这篇综述中，我们将介绍通过 JAK/STAT 信号转导促进 IBD 发病机制的主要细胞因子和细胞因子，并强调 JAK/STAT 在这方面的综合功能以及它们在不同细胞和过程中的不同作用。此外，我们将解释 JAK/STAT 信号转导在 CAC 中的作用，并讨论目前和未来干扰 JAK/STAT 信号转导的 IBD 治疗方法。
