In the gut, cathelicidin-related antimicrobial peptide (CRAMP) has been largely described for its anti-infective activities. With an increasing recognition of its immune regulatory effects in extra-intestinal diseases, the role of CRAMP in gluten-induced small intestinal enteropathy celiac disease remains unknown. This study aimed to investigate the unexplored role of CRAMP in celiac disease. By applying a mouse model of gluten-induced enteropathy (GIE) recapitulating small intestinal enteropathy of celiac disease, we observed defective CRAMP production in duodenal epithelium during GIE. CRAMP-deficient mice were susceptible to the development of GIE. Exogenous CRAMP corrected gliadin-triggered epithelial dysfunction and promoted regulatory immune responses at the intestinal mucosa. Additionally, GIE-associated gut dysbiosis with enriched Pseudomonas aeruginosa and production of the protease LasB contributed to defective intestinal CRAMP production. These results highlight microbiota-CRAMP axis in the modulation of barrier function and immune responses in GIE. Hence, modulating CRAMP may represent a therapeutic strategy for celiac disease.

中文翻译：

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肠道微生物群-CRAMP轴塑造膳食麸质诱发肠病的肠道屏障功能和免疫反应

在肠道中，抗菌素相关抗菌肽 (CRAMP) 因其抗感染活性而被广泛描述。随着人们越来越认识到其在肠外疾病中的免疫调节作用，CRAMP 在麸质诱导的小肠肠病乳糜泻中的作用仍不清楚。本研究旨在探讨 CRAMP 在乳糜泻中尚未探索的作用。通过应用谷蛋白诱导性肠病 (GIE) 小鼠模型来概括乳糜泻的小肠肠病，我们观察到 GIE 期间十二指肠上皮中 CRAMP 产生缺陷。CRAMP 缺陷的小鼠容易发生 GIE。外源性 CRAMP 纠正了麦醇溶蛋白引发的上皮功能障碍，并促进肠粘膜的调节性免疫反应。此外，与 GIE 相关的肠道菌群失调以及铜绿假单胞菌的富集和蛋白酶 LasB 的产生导致了肠道 CRAMP 产生缺陷。这些结果强调了微生物群-CRAMP 轴在 GIE 屏障功能和免疫反应调节中的作用。因此，调节 CRAMP 可能代表乳糜泻的一种治疗策略。