Paneth cell defensins: key effector molecules of innate immunity
Paneth cell defensins: key effector molecules of innate immunity
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DOI：
10.1042/bst0340263
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发表时间：
2006-04-01
影响因子：
3.9
通讯作者：
Bevins, CL
中科院分区：
文献类型：
--
作者：
Bevins, CL
抗菌肽是先天免疫的基本效应分子，几乎所有被研究的生物都利用于宿主防御。这些基因编码的肽对多种细菌和其他微生物具有直接的抗生素活性。在人类和其他哺乳动物中，防御素是这类肽的主要类别。在哺乳动物的小肠中，位于肠壁隐窝内陷底部的专门分泌上皮细胞Paneth细胞产生防御素和其他抗生素蛋白。最近对小鼠模型的研究为肠道防御素在防御肠道内食物和水传播的病原体方面发挥关键作用的假设提供了强有力的支持。其他研究表明，肠道共生菌是遗传易感人群中IBD（炎症性肠病）发病的关键因素。最近的研究提供证据表明，Paneth细胞防御素的表达减少可能是IBD亚组回肠克罗恩病发病的关键因素。未来研究进一步明确Paneth细胞防御素的功能和调控，将增强我们对正常小肠生理的认识，并可能有助于更好地理解肠道炎症和感染性疾病的发病机制。这些知识可能提供新的治疗靶点和策略。
Antimicrobial peptides are fundamental effector molecules of innate immunity, utilized in host defence by virtually all organisms studied. These gene-encoded peptides have direct antibiotic activity against a wide range of bacteria and other microbes. in humans and other mammals, defensins are a predominant class of such peptides. In the mammalian small intestine, Paneth cells, specialized secretory epithelial cells located at the base of the crypt invaginations lining the intestinal wall, produce defensins and other antibiotic proteins. Recent investigations in murine models provide compelling support for the hypothesis that enteric defensins play a pivotal role in defence from food- and water-borne pathogens in the intestinal lumen. Investigations by others indicate that intestinal commensal bacteria are key factors in the pathogenesis of IBD (inflammatory bowel disease) in genetically susceptible humans. Recent studies provide evidence that reduced expression of Paneth cell defensins may be a key factor in the pathogenesis of ileal Crohn's disease, a subgroup of IBD. Future studies to further define the function and regulation of Paneth cell defensins will enhance our understanding of normal small bowel physiology, and probably contribute to a better understanding of the pathogenesis of inflammatory and infectious diseases of the bowel. Such knowledge may provide new therapeutic targets and strategies.