2024年5月13日，美国华盛顿大学医学院Jakob von Moltke课题组在《免疫》杂志发表论文，报道了簇细胞来源的乙酰胆碱促进上皮氯离子分泌和肠蠕虫清除。

该团队发现簇细胞的激活能迅速诱导小肠上皮氯离子分泌。这种反应需要簇细胞的感觉功能和簇细胞来源的乙酰胆碱(ACh)，它直接作用于邻近的上皮细胞以刺激氯化物分泌，而不依赖于神经元。簇细胞诱导的最大氯化物分泌与蠕虫的免疫限制相一致，尽管正常的2型炎症，但缺乏簇细胞来源的乙酰胆碱的小鼠清除延迟。他们发现了一个上皮内反应单元，使乙酰胆碱和簇细胞感应与邻近上皮细胞的分泌防御结合起来。

据了解，上皮细胞分泌氯来调节粘膜屏障的水释放，支持稳态水合作用和“哭泣”反应，这对针对寄生虫(蠕虫)的2型免疫防御至关重要。小肠上皮簇细胞具有感知蠕虫的作用，并释放细胞因子和脂质来激活2型免疫细胞，但它们是否调节上皮细胞的分泌尚不清楚。

附：英文原文

Title: Tuft cell-derived acetylcholine promotes epithelial chloride secretion and intestinal helminth clearance

Author: Tyler E. Billipp, Connie Fung, Lily M. Webeck, Derek B. Sargent, Matthew B. Gologorsky, Zuojia Chen, Margaret M. McDaniel, Darshan N. Kasal, John W. McGinty, Kaitlyn A. Barrow, Lucille M. Rich, Alessio Barilli, Mark Sabat, Jason S. Debley, Chuan Wu, Richard Myers, Michael R. Howitt, Jakob von Moltke

Issue&Volume: 2024-05-13

Abstract: Epithelial cells secrete chloride to regulate water release at mucosal barriers, supportingboth homeostatic hydration and the “weep” response that is critical for type 2 immunedefense against parasitic worms (helminths). Epithelial tuft cells in the small intestinesense helminths and release cytokines and lipids to activate type 2 immune cells,but whether they regulate epithelial secretion is unknown. Here, we found that tuftcell 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 chloridesecretion, independent of neurons. Maximal tuft cell-induced chloride secretion coincidedwith immune restriction of helminths, and clearance was delayed in mice lacking tuftcell-derived ACh, despite normal type 2 inflammation. Thus, we have uncovered an epithelium-intrinsicresponse unit that uses ACh to couple tuft cell sensing to the secretory defensesof neighboring epithelial cells.

DOI: 10.1016/j.immuni.2024.03.023

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00144-4