作为一类阳离子宿主防御肽家族，防御素主要由Paneth细胞、中性粒细胞和上皮细胞合成，对宿主防御发挥重要作用。近年来，防御素在先天免疫中的生物学功能、结构与活性关系、作用机制和治疗潜力备受关注。为突出防御素在人类和动物健康中的关键研究，我们首先描述了其研究历史、结构特征、进化以及抗微生物机制。接下来，我们详细介绍了防御素在免疫稳态、趋化性、黏膜屏障功能、肠道微生物调控、肠道发育和细胞死亡调控中的作用。此外，我们还讨论了防御素在各种疾病中的临床相关性和治疗潜力，包括感染性疾病、炎症性肠病、糖尿病和肥胖症、慢性炎症性肺疾病、牙周炎和癌症。最后，我们总结了防御素营养依赖调控的当前认识，包括脂肪酸、氨基酸、微量元素、植物提取物和益生菌，并考虑了这种调控的临床应用。总之，本综述总结了防御素的各种生物学功能、作用机制和潜在临床意义，同时提出了基于防御素的治疗方法发展中的挑战，为了解其生物学和潜在临床应用提供了关键见解。©2023年 四川大学华西医院。

As a family of cationic host defense peptides, defensins are mainly synthesized by Paneth cells, neutrophils, and epithelial cells, contributing to host defense. Their biological functions in innate immunity, as well as their structure and activity relationships, along with their mechanisms of action and therapeutic potential, have been of great interest in recent years. To highlight the key research into the role of defensins in human and animal health, we first describe their research history, structural features, evolution, and antimicrobial mechanisms. Next, we cover the role of defensins in immune homeostasis, chemotaxis, mucosal barrier function, gut microbiota regulation, intestinal development and regulation of cell death. Further, we discuss their clinical relevance and therapeutic potential in various diseases, including infectious disease, inflammatory bowel disease, diabetes and obesity, chronic inflammatory lung disease, periodontitis and cancer. Finally, we summarize the current knowledge regarding the nutrient-dependent regulation of defensins, including fatty acids, amino acids, microelements, plant extracts, and probiotics, while considering the clinical application of such regulation. Together, the review summarizes the various biological functions, mechanism of actions and potential clinical significance of defensins, along with the challenges in developing defensins-based therapy, thus providing crucial insights into their biology and potential clinical utility.© 2023. West China Hospital, Sichuan University.