PDF(Pubmed)
Abstract：
Antimicrobial proteins contribute to host-microbiota interactions and are associated with inflammatory bowel disease (IBD), but our understanding on antimicrobial protein diversity and functions remains incomplete. Ribonuclease 4 (Rnase4) is a potential antimicrobial protein with no known function in the intestines. Here we find that RNASE4 is expressed in intestinal epithelial cells (IEC) including Paneth and goblet cells, and is detectable in human and mouse stool. Results from Rnase4-deficient mice and recombinant protein suggest that Rnase4 kills Parasutterella to modulate intestinal microbiome, thereby enhancing indoleamine-2,3-dioxygenase 1 (IDO1) expression and subsequently kynurenic and xanthurenic acid production in IECs to reduce colitis susceptibility. Furthermore, deceased RNASE4 levels are observed in the intestinal tissues and stool from patients with IBD, correlating with increased stool Parasutterella. Our results thus implicate Rnase4 as an intestinal antimicrobial protein regulating gut microbiota and metabolite homeostasis, and as a potential diagnostic biomarker and therapeutic target for IBD.
摘要：
抗微生物蛋白有助于宿主-微生物群相互作用，并与炎症性肠病（IBD）相关。但是我们对抗菌蛋白多样性和功能的理解仍然不完整。核糖核酸酶4（Rnase4）是一种潜在的抗菌蛋白，在肠道中没有已知的功能。在这里，我们发现RNASE4在肠上皮细胞（IEC）中表达，包括Paneth和杯状细胞，并且在人类和小鼠粪便中可以检测到。来自Rnase4缺陷小鼠和重组蛋白的结果表明，Rnase4杀死了副茎以调节肠道微生物组，从而增强IECs中吲哚胺-2,3-双加氧酶1（IDO1）的表达，并随后增强犬尿氨酸和黄酮酸的产生，以降低结肠炎的易感性。此外，在IBD患者的肠组织和粪便中观察到死亡的RNASE4水平，与粪便增加有关。因此，我们的结果暗示Rnase4是一种肠道抗菌蛋白，可调节肠道微生物群和代谢物稳态，作为IBD的潜在诊断生物标志物和治疗靶点。
