Gut microbiota-CRAMP axis shapes intestinal barrier function and immune responses in dietary gluten-induced enteropathy.
Gut microbiota-CRAMP axis shapes intestinal barrier function and immune responses in dietary gluten-induced enteropathy.
复制标题
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
DOI：
10.15252/emmm.202114059
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发表时间：
2021-08-09
影响因子：
11.1
通讯作者：
Sun J
中科院分区：
文献类型：
--
作者：
Ren Z;Pan LL;Huang Y;Chen H;Liu Y;Liu H;Tu X;Liu Y;Li B;Dong X;Pan X;Li H;Fu YV;Agerberth B;Diana J;Sun J
在肠道中，cathelicidin相关的抗菌肽（CRAMP）已被大量描述为具有抗感染活性。随着越来越多的人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然未知。本研究旨在研究CRAMP在乳糜泻中未探索的作用。通过应用模拟乳糜泻小肠肠病的麸质诱导性肠病（GIE）小鼠模型，我们观察到GIE期间十二指肠上皮细胞中CRAMP产生缺陷。CRAMP缺陷型小鼠易发生GIE。外源性CRAMP纠正了麦胶蛋白引发的上皮功能障碍，并促进了肠粘膜的调节性免疫反应。此外，GIE相关的肠道生态失调与富集的铜绿假单胞菌和蛋白酶LasB的产生促成了有缺陷的肠道CRAMP产生。这些结果突出了微生物群-CRAMP轴在GIE中调节屏障功能和免疫反应。因此，调节CRAMP可能代表乳糜泻的治疗策略。cathelicidin相关的抗菌肽（CRAMP）在肠道微生物群的影响下在饮食性谷蛋白诱导的肠病（GIE）中的保护作用已经确立，为乳糜泻的治疗策略提供了独特的见解。
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. A protective role of cathelicidin‐related antimicrobial peptide (CRAMP) under the influence of gut microbiota in dietary gluten‐induced enteropathy (GIE) is established to provide unique insights into the therapeutic strategy for celiac disease.