Department of Physiology, Biophysics and Neurosciences, Cinvestav Zacatenco, Mexico City CP 07360, Mexico; and.
Department of Molecular Biomedicine, Cinvestav Zacatenco, Mexico City CP 07360, Mexico.
J Immunol. 2019 Feb 15;202(4):1239-1249. doi: 10.4049/jimmunol.1801060. Epub 2019 Jan 9.
A single layer of polarized epithelial cells lining the colonic mucosa create a semipermeable barrier indispensable for gut homeostasis. The role of intestinal epithelial cell (IEC) polarization in the maintenance of the epithelial homeostasis and in the development of inflammatory bowel diseases is not fully understood. In this review, now we report that IEC polarization plays an essential role in the regulation of IL-6/STAT3 signaling in the colonic mucosa. Our results demonstrate that autocrine STAT3 activation in IECs is mediated by the apical secretion of IL-6 in response to the basolateral stimulation with IFN-γ. This process relies on the presence of functional, IFN-γ-producing CD4 T cells. In the absence of basolateral IFN-γ, the compartmentalization of the IL-6/STAT3 signaling is disrupted, and STAT3 is activated mainly in macrophages. Thus, in this study, we show that during inflammation, IFN-γ regulates IL-6/STAT3 signaling in IEC in the colonic mucosa.
单层极化的肠上皮细胞排列在结肠黏膜表面，形成半透性屏障，对于肠道内环境的稳定至关重要。肠道上皮细胞（IEC）极化在维持上皮细胞稳态和炎症性肠病（IBD）的发生发展中的作用尚未完全阐明。在本综述中，我们报告称，IEC 极化在调节结肠黏膜中 IL-6/STAT3 信号通路中发挥着重要作用。我们的结果表明，IEC 中自分泌 STAT3 的激活是由 IL-6 的顶端分泌介导的，这是对 IFN-γ 基底外侧刺激的反应。这一过程依赖于功能正常、能产生 IFN-γ 的 CD4 T 细胞的存在。在缺乏基底外侧 IFN-γ的情况下，IL-6/STAT3 信号通路的分隔被破坏，STAT3 主要在巨噬细胞中被激活。因此，在这项研究中，我们表明在炎症过程中，IFN-γ 调节结肠黏膜中 IEC 的 IL-6/STAT3 信号通路。
