The role of innate immunity in inflammatory bowel disease

本研究的目的是确定抗菌肽在正常和炎症肠道中的作用，并通过重组防御素调节先天免疫来探索炎症性肠病的潜在治疗选择。结果表明，1)健康志愿者、克罗恩病（CD）和溃疡性结肠炎患者小肠隐窝中表达的人防御素5 (HD-5) mRNA和蛋白；2)CD患者的防御素和toll样受体基因谱与健康志愿者不同；3)CD患者的HD-5杀菌活性较健康志愿者减弱。4)从CD患者体内提取的proHD-5的氨基酸序列中，部分CD患者的HD-5的二硫桥消失，提示在炎症性肠病中，HD-5的功能受到翻译后修饰的调节。5)重组HD-5对胰蛋白酶和蛋白酶稳定，4%葡聚糖硫酸钠处理后小鼠的存活率提高。综上所述，本研究提供了HD-5在正常和炎症肠道先天免疫中的重要作用，为炎症性肠病提供了一种针对先天免疫受损的新的治疗选择。

The aim of this study was to determine the role of antibacterial peptides in normal and inflamed intestine, and explore a potential therapeutic option for inflammatory bowel disease through the regulation of innate immunity by recombinant defensins.As results, this study demonstrated that, 1) human defensin 5 (HD-5) mRNA and protein expressed in small intestinal crypts of healthy volunteers and patients with Crohn's disease (CD) and ulcerative colitis, 2) gene profiles of defensins and toll-like receptors in the patients with CD was different from that in healthy volunteers, 3) bactericidal activity of HD-5 derived from the patients with CD was attenuated compared with that of healthy volunteers, 4) whereas the amino acid sequence of proHD-5 extracted from the patients with CD, disulphide bridges of the HD-5 of some CD patients were disappeared, suggesting that the function of HD-5 was regulated by a post-translational modification in inflammatory bowel disease and 5) recombinant HD-5, which was stable for trypsins and proteases, improved the survival rate of mice treated with 4% dextran sodium sulfate-treated.In summary, this study provided an important role of HD-5 in innate immunity of normal and inflamed inteastine, and proposed a novel therapeutic option for inflammatory bowel disease, targeting the impaired innate immunity.