Cell:IL-18抑制杯状细胞成熟并促进粘膜损伤

Cell

2015-12-03Article

30.410

影响因子

原标题:上皮IL-8的平衡控制结肠炎中的屏障功能

① 肠道屏障粘膜功能依赖于杯状细胞生成的保护性黏液层,后者的损伤是IBD的标记之一;② 在结肠炎小鼠模型中发现,IL-18在驱动病理性粘膜屏障完整性破坏中十分关键;③ 肠道上皮细胞中IL-18或其受体IL-18R1的缺失,在小鼠结肠炎及粘膜损伤中起到保护作用,而缺失IL-18 的负向调节因子IL18BP导致与成熟杯状细胞丢失相关的严重结肠炎;④ IL-18通过调节转录程序指导杯状细胞的发育而抑制杯状细胞的成熟。

结肠炎 杯状细胞 肠道粘膜屏障 粘液层

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Title:
Epithelial IL-18 Equilibrium Controls Barrier Function in Colitis

DOI:
10.1016/j.cell.2015.10.072

Abstract & Authors展开

Abstract:
The intestinal mucosal barrier controlling the resident microbiome is dependent on a protective mucus layer generated by goblet cells, impairment of which is a hallmark of the inflammatory bowel disease, ulcerative colitis. Here, we show that IL-18 is critical in driving the pathologic breakdown of barrier integrity in a model of colitis. Deletion of Il18 or its receptor Il18r1 in intestinal epithelial cells (Δ/EC) conferred protection from colitis and mucosal damage in mice. In contrast, deletion of the IL-18 negative regulator Il18bp resulted in severe colitis associated with loss of mature goblet cells. Colitis and goblet cell loss were rescued in Il18bp−/−;Il18rΔ/EC mice, demonstrating that colitis severity is controlled at the level of IL-18 signaling in intestinal epithelial cells. IL-18 inhibited goblet cell maturation by regulating the transcriptional program instructing goblet cell development. These results inform on the mechanism of goblet cell dysfunction that underlies the pathology of ulcerative colitis.

All Authors:
Roni Nowarski, , Richard A Flavell

First Authors:
Roni Nowarski

Correspondence:
Richard A Flavell

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