The Interplay between Defensins and Microbiota in Crohn's Disease.
The Interplay between Defensins and Microbiota in Crohn's Disease.
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DOI：
10.1155/2017/8392523
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发表时间：
2017
影响因子：
4.6
通讯作者：
Pero R
中科院分区：
文献类型：
--
作者：
Coretti L;Natale A;Cuomo M;Florio E;Keller S;Lembo F;Chiariotti L;Pero R
克罗恩病（CD）是一种肠粘膜慢性炎症，以急性复发和缓解期为特征。根据受影响的特定区域，CD被分类为回肠CD或结肠CD。人们普遍认为肠道微生物群参与了病理学的发病。事实上，对肠道微生物群组分的免疫耐受性降低和肠道屏障炎症是CD患者的典型特征。几项研究表明，与对照组相比，CD患者的肠道抗菌肽（AMP）表达缺陷，特别是防御素。在回肠CD中观察到α-防御素减少，而在结肠CD中β-防御素增加。除了免疫学基础之外，该疾病还经常与包括NOD 2基因突变在内的遗传改变相关。目前正在研究几种治疗策略，以避免在CD中观察到的功能障碍。这些包括使用递送系统来施用内源性AMP和可以改善CD严重性的肽模拟物的工程化。在这篇综述中，防御素在CD中发挥的作用和旨在克服细菌耐药性的策略将被讨论。
Crohn's disease (CD) is a chronic inflammation of the intestinal mucosa, characterized by periods of acute recurrence and remission. Depending on the specific region affected, CD is classified as ileal CD or colonic CD. It is largely accepted that the intestinal microbiota is involved in the onset of the pathology. Indeed, a reduced immune tolerance to components of the intestinal commensal microbiota and inflammation of the intestinal barrier typifies patients with CD. Several studies have shown defective expression of intestinal antimicrobial peptides (AMPs) in patients with CD compared to controls, particularly defensins. A reduction in α-defensins is observed in ileal CD, while β-defensins are increased in colonic CD. In addition to an immunological basis, the disease is frequently associated with genetic alterations including mutations of NOD2 gene. Several therapeutic strategies to circumvent the dysfunction observed in CD are currently under investigation. These include the use of delivery systems to administer endogenous AMPs and the engineering of peptidomimetics that could ameliorate the severity of CD. In this review, the role defensins play in CD and the strategies aimed at overcoming bacterial resistance will be discussed.