Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, England, UK.
J Exp Med. 2012 Aug 27;209(9):1595-609. doi: 10.1084/jem.20111453. Epub 2012 Aug 13.
Although very high levels of interleukin (IL)-1β are present in the intestines of patients suffering from inflammatory bowel diseases (IBD), little is known about the contribution of IL-1β to intestinal pathology. Here, we used two complementary models of chronic intestinal inflammation to address the role of IL-1β in driving innate and adaptive pathology in the intestine. We show that IL-1β promotes innate immune pathology in Helicobacter hepaticus-triggered intestinal inflammation by augmenting the recruitment of granulocytes and the accumulation and activation of innate lymphoid cells (ILCs). Using a T cell transfer colitis model, we demonstrate a key role for T cell-specific IL-1 receptor (IL-1R) signals in the accumulation and survival of pathogenic CD4(+) T cells in the colon. Furthermore, we show that IL-1β promotes Th17 responses from CD4(+) T cells and ILCs in the intestine, and we describe synergistic interactions between IL-1β and IL-23 signals that sustain innate and adaptive inflammatory responses in the gut. These data identify multiple mechanisms through which IL-1β promotes intestinal pathology and suggest that targeting IL-1β may represent a useful therapeutic approach in IBD.
尽管患有炎症性肠病 (IBD) 的患者的肠道中存在非常高水平的白细胞介素 (IL)-1β，但对于 IL-1β 对肠道病理学的贡献知之甚少。在这里，我们使用两种互补的慢性肠道炎症模型来解决 IL-1β 在驱动肠道固有和适应性病理中的作用。我们表明，IL-1β 通过增强粒细胞的募集以及固有淋巴细胞 (ILC) 的积累和激活来促进幽门螺杆菌触发的肠道炎症中的固有免疫病理。使用 T 细胞转移结肠炎模型，我们证明了 T 细胞特异性 IL-1 受体 (IL-1R) 信号在致病性 CD4(+) T 细胞在结肠中的积累和存活中的关键作用。此外，我们表明 IL-1β 促进了肠道中 CD4(+) T 细胞和 ILC 产生 Th17 反应，并且我们描述了 IL-1β 和 IL-23 信号之间的协同相互作用，这些相互作用维持了肠道中的固有和适应性炎症反应。这些数据确定了 IL-1β 促进肠道病理学的多种机制，并表明靶向 IL-1β 可能是治疗 IBD 的一种有用方法。
