PDF(Pubmed)
Abstract：
Epithelial cells secrete chloride to regulate water release at mucosal barriers, supporting both homeostatic hydration and the \"weep\" response that is critical for type 2 immune defense against parasitic worms (helminths). Epithelial tuft cells in the small intestine sense helminths and release cytokines and lipids to activate type 2 immune cells, but whether they regulate epithelial secretion is unknown. Here, we found that tuft cell activation rapidly induced epithelial chloride secretion in the small intestine. This response required tuft cell sensory functions and tuft cell-derived acetylcholine (ACh), which acted directly on neighboring epithelial cells to stimulate chloride secretion, independent of neurons. Maximal tuft cell-induced chloride secretion coincided with immune restriction of helminths, and clearance was delayed in mice lacking tuft cell-derived ACh, despite normal type 2 inflammation. Thus, we have uncovered an epithelium-intrinsic response unit that uses ACh to couple tuft cell sensing to the secretory defenses of neighboring epithelial cells.
摘要：
上皮细胞分泌氯化物调节粘膜屏障的水释放，支持稳态水合和“哭泣”反应，这对于2型免疫防御寄生虫（蠕虫）至关重要。小肠中的上皮簇细胞感知蠕虫并释放细胞因子和脂质以激活2型免疫细胞，但它们是否调节上皮分泌尚不清楚。这里,我们发现，簇绒细胞活化迅速诱导小肠上皮氯化物分泌。这种反应需要簇绒细胞感觉功能和簇绒细胞衍生的乙酰胆碱（ACh），直接作用于邻近的上皮细胞以刺激氯化物分泌，独立于神经元。最大簇绒细胞诱导的氯化物分泌与蠕虫的免疫限制相吻合，在缺乏簇绒细胞来源的ACh的小鼠中，清除延迟，尽管正常的2型炎症。因此，我们发现了一个上皮固有反应单元，该单元使用ACh将簇绒细胞感应与相邻上皮细胞的分泌防御相耦合。
