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VAMP8-mediated MUC2 mucin exocytosis from colonic goblet cells maintains innate intestinal homeostasis.
Nature Communications ( IF 14.7 ) Pub Date : 2019-09-20 , DOI: 10.1038/s41467-019-11811-8
Steve Cornick 1 , Manish Kumar 1 , France Moreau 1 , Herbert Gaisano 2 , Kris Chadee 1
Affiliation  

The mucus layer is the first line of innate host defense in the gut that protects the epithelium by spatially separating commensal bacteria. MUC2 mucin is produced and stored by goblet cells that is constitutively exocytosed or hyper secreted upon sensing a threat. How coordinated mucus exocytosis maintains homeostasis in the intestinal epithelium and modulates the immunological landscape remains elusive. Here we describe how the vesicle SNARE protein VAMP8 coordinates mucin exocytosis from goblet cells. Vamp8-/- exhibit a mild pro-inflammatory state basally due to an altered mucus layer and increased encounters with microbial antigens. Microbial diversity shifts to a detrimental microbiota with an increase abundance of pathogenic and mucolytic bacteria. To alleviate the heavy microbial burden and inflammatory state basally, Vamp8-/- skews towards tolerance. Despite this, Vamp8-/- is highly susceptible to both chemical and infectious colitis demonstrating the fragility of the intestinal mucosa without proper mucus exocytosis mechanisms.

中文翻译:

VAMP8介导的来自结肠杯状细胞的MUC2粘蛋白胞吐作用保持了先天肠道的动态平衡。

粘液层是肠道中先天宿主防御的第一线,它通过在空间上分隔共生细菌来保护上皮。MUC2粘蛋白由杯状细胞产生和储存,杯状细胞在感知到威胁后会组成性地胞吐或分泌过多。协调的粘液胞吐作用如何在肠道上皮中维持体内稳态并调节免疫学状况仍然难以捉摸。在这里,我们描述了囊泡网罗蛋白VAMP8如何协调杯状细胞黏蛋白的胞吐作用。由于改变的粘液层和与微生物抗原的接触增加,Vamp8-/-基本表现出轻度的促炎状态。随着致病菌和粘液溶解菌的丰度增加,微生物多样性转移到有害的微生物群。为了从根本上减轻沉重的微生物负担和炎症状态,Vamp8-/-偏向容差。尽管如此,Vamp8-/-高度易受化学性和感染性结肠炎的影响,显示出肠粘膜的脆弱性而没有适当的粘液胞吐机制。
更新日期:2019-09-21
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