法国蒙彼利埃大学Philippe Jay等研究人员合作发现，簇细胞乙酰胆碱被释放到肠腔以促进抗蠕虫免疫。2024年5月13日，《免疫》杂志在线发表了这项成果。

据研究人员介绍，寄生蠕虫感染后，活化的肠绒毛细胞会分泌白细胞介素-25（IL-25），从而启动2型免疫反应，其间固有层2型先天性淋巴细胞（ILC2）会产生IL-13。这将导致上皮重塑，包括簇细胞增生，其功能尚不清楚。

研究人员发现了簇细胞的胆碱能效应功能，它们是唯一表达胆碱乙酰转移酶（ChAT）的上皮细胞。在寄生虫感染期间，上皮细胞特异性缺失ChAT的小鼠的蠕虫负担、体能和粪便中的虫卵数量都有所增加，尽管2型免疫反应与之相当。从机制上讲，IL-13扩增的簇细胞会向肠腔释放乙酰胆碱（ACh）。

最后，研究人员证明了乙酰胆碱对蠕虫的直接影响，它通过蠕虫表达的毒蕈碱乙酰胆碱受体降低了蠕虫的繁殖力。因此，簇细胞是初始小鼠的哨兵，它们在蠕虫感染时的放大提供了额外的2型免疫反应效应器功能。

附：英文原文

Title: Tuft cell acetylcholine is released into the gut lumen to promote anti-helminth immunity

Author: Marième Ndjim, Imène Gasmi, Fabien Herbert, Charlène Joséphine, Julie Bas, Ali Lamrani, Nathalie Coutry, Sylvain Henry, Valérie S. Zimmermann, Valérie Dardalhon, Marta Campillo Poveda, Evgenia Turtoi, Steeve Thirard, Luc Forichon, Alicia Giordano, Claire Ciancia, Zeinab Homayed, Julie Pannequin, Collette Britton, Eileen Devaney, Tom N. McNeilly, Sylvie Berrard, Andrei Turtoi, Rick M. Maizels, Franois Gerbe, Philippe Jay

Issue&Volume: 2024-05-13

Abstract: Upon parasitic helminth infection, activated intestinal tuft cells secrete interleukin-25 (IL-25), which initiates a type 2 immune response during which lamina propria type 2 innate lymphoid cells (ILC2s) produce IL-13. This causes epithelial remodeling, including tuft cell hyperplasia, the function of which is unknown. We identified a cholinergic effector function of tuft cells, which are the only epithelial cells that expressed choline acetyltransferase (ChAT). During parasite infection, mice with epithelial-specific deletion of ChAT had increased worm burden, fitness, and fecal egg counts, even though type 2 immune responses were comparable. Mechanistically, IL-13-amplified tuft cells release acetylcholine (ACh) into the gut lumen. Finally, we demonstrated a direct effect of ACh on worms, which reduced their fecundity via helminth-expressed muscarinic ACh receptors. Thus, tuft cells are sentinels in naive mice, and their amplification upon helminth infection provides an additional type 2 immune response effector function.

DOI: 10.1016/j.immuni.2024.04.018

Source: https://www.cell.com/immunity/fulltext/S1074-7613(24)00223-1