Innate immune signalling at intestinal mucosal surfaces: a fine line between host protection and destruction
Innate immune signalling at intestinal mucosal surfaces: a fine line between host protection and destruction
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DOI：
10.1097/mog.0b013e32830c4341
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发表时间：
2008-11-01
影响因子：
2.5
通讯作者：
Cario, Elke
中科院分区：
文献类型：
--
作者：
Cario, Elke
综述目的新出现的证据强调，由共生体驱动的不适当的先天免疫反应导致遗传易感宿主中慢性炎症性肠病的发病机制。本综述重点关注定义最近描述的机制功能，先天免疫信号装置通过这些功能塑造健康和疾病中肠道的粘膜稳态。最新发现共生诱导的先天免疫信号主动驱动至少六种主要的相互依赖的功能来控制健康肠粘膜的稳态：1）屏障保护，2）抑制细胞凋亡和炎症， 3）加速伤口修复和组织再生，4）通过自噬和其他抗菌防御排除有害病原体，同时5）维持对无害共生体的免疫耐受，以及6）与适应性免疫的联系。这种和平且互利的宿主共生关系的任何干扰都可能导致先天免疫信号失衡，从而导致慢性肠道炎症和炎症性肠病中相关的肿瘤发生。总结最近的进展强调了先天免疫的复杂机制和功能多样性，它矛盾地介导了肠粘膜的保护性和破坏性反应。相关信号传导靶标可能为治疗炎症性肠病和炎症相关癌症提供新的治疗方法。
Purpose of reviewEmerging evidence underscores that inappropriate innate immune responses driven by commensals contribute to the pathogenesis of chronic inflammatory bowel diseases in genetically susceptible hosts. The present review focuses on defining the recently described mechanistic functions through which the innate immune signalling apparatus shapes mucosal homeostasis of the intestine in health and disease.Recent findingsCommensal-induced innate immune signalling actively drives at least six major interdependent functions to control homeostasis in the healthy intestinal mucosa: 1) barrier preservation, 2) inhibition of apoptosis and inflammation, 3) acceleration of wound repair and tissue regeneration, 4) exclusion of harmful pathogens through autophagy and other antimicrobial defenses, while 5) maintaining immune tolerance towards harmless commensals, and 6) linkage to adaptive immunity. Any disturbance of this peaceful and mutually beneficial host-commensal relationship may imbalance innate immune signalling, which predisposes to chronic intestinal inflammation and associated tumourigenesis in inflammatory bowel diseases.SummaryRecent advances have highlighted the complex mechanistics and functional diversity of innate immunity that paradoxically mediate both protective and destructive responses in the intestinal mucosa. Related signalling targets may offer novel therapeutic approaches in the treatment of inflammatory bowel diseases and inflammation-related cancer.