Sardi Claudia, Luchini Patrizia, Emanuelli Andrea, Giannoni Amedeo, Martini Elisa, Manara Lucia M, Sfondrini Lucia, Kallikourdis Marinos, Sommariva Michele, Rumio Cristiano
Department of Pharmacology and Biomolecular Sciences, University of Milan, Via Trentacoste 2, Milan, 20133, Italy.
Adaptive Immunity Lab, Humanitas Clinical and Research Center, Via Manzoni 56, Rozzano, 20089, Italy.
Microsc Res Tech. 2017 Jun;80(6):563-569. doi: 10.1002/jemt.22831. Epub 2017 Jan 17.
Several studies support the role of Western-style diet (WD) in inflammatory bowel disease (IBD). Toll-like receptors/NOD-like receptors (TLRs/NLRs) are important to maintain a healthy epithelium as well as inducing inflammation. Given that dietary factors influence IBD development, that epithelial dysfunction is thought to be involved in initiating intestinal inflammation and that TLR-NLR are involved in maintenance of the functionality of intestinal epithelium as well as in regulating inflammation, we decided to examine the role of TLR signals in the triggering events that lead to alteration of the small intestinal epithelium associated to consumption of WD. C57BL/6J mice deficient for TLR2, 4, 9, or NOD2 and wild-type (WT) were fed a WD or a standard diet for 3 months. The effects of WD on small intestinal samples were evaluated by histological and immunohistochemical analysis. After 3 months, WD modifies the morphology and the organization of the small intestine in TLR9 KO mice compared with WT mice and the others TLRs. The most interesting change involved the expression of proliferative and differentiation markers of WNT signaling, Ki67 and FzD5. Mice deficient in TLR2, 4, and NOD2 have a significant reduction in the proliferative cell numbers but do not show any signs of histological alterations. Our results suggest that TLR9 is an important protective factor in intestinal epithelial homeostasis and provide new insights into an unrecognized role of TLR9 signaling in the small intestinal mucosa dysfunction associated with WD.
多项研究支持西式饮食（WD）在炎症性肠病（IBD）中的作用。Toll样受体/核苷酸结合寡聚化结构域样受体（TLRs/NLRs）对于维持健康的上皮细胞以及引发炎症都很重要。鉴于饮食因素会影响IBD的发展，上皮功能障碍被认为参与了肠道炎症的起始，并且TLR-NLR参与了肠道上皮功能的维持以及炎症调节，我们决定研究TLR信号在导致与WD摄入相关的小肠上皮改变的触发事件中的作用。对缺乏TLR2、4、9或NOD2的C57BL/6J小鼠和野生型（WT）小鼠喂食WD或标准饮食3个月。通过组织学和免疫组织化学分析评估WD对小肠样本的影响。3个月后，与WT小鼠和其他TLRs相比，WD改变了TLR9基因敲除小鼠小肠的形态和组织结构。最有趣的变化涉及WNT信号的增殖和分化标志物Ki67和FzD5的表达。缺乏TLR2、4和NOD2的小鼠增殖细胞数量显著减少，但未显示出任何组织学改变的迹象。我们的结果表明，TLR9是肠道上皮稳态中的一个重要保护因子，并为TLR9信号在与WD相关的小肠黏膜功能障碍中未被认识的作用提供了新的见解。
