再生生物学中一个基本且未解决的问题是组织在受伤后如何恢复稳态。解答这个问题对于理解炎症性肠病和癌症等慢性疾病的病因至关重要。我们利用果蝇中肠来进行研究，并发现在再生过程中，一种名为胆碱能神经元的亚群会触发肠上皮细胞（肠道上皮细胞）之间的钙离子电流，促进返回稳态。我们发现，肠道上皮中共同的胆碱能酶乙酰胆碱酯酶的下调使得来自特定的TNF/Egr敏感胆碱能神经元的乙酰胆碱能够激活受到神经支配的肠道上皮细胞中的尼古丁酸受体。这种激活会引发高浓度的钙离子，通过Inx2/Inx7间隙链接在上皮中扩散，促进上皮细胞的成熟，并随之降低细胞增殖和炎症。破坏这个过程会导致离子失衡、Yki/Yap激活、细胞死亡以及炎性细胞因子增加，这些症状类似于炎症性肠病。总的来说，共同存在的胆碱能途径促进了愈合肠道上皮的钙离子电流。我们的发现证明了依赖于神经和生物电的肠道再生，并推进了我们对组织在受伤后如何恢复稳态的理解。© 2023.本文作者以独家许可授权给斯普林格自然有限公司。

A fundamental and unresolved question in regenerative biology is how tissues return to homeostasis after injury. Answering this question is essential for understanding the etiology of chronic disorders such as inflammatory bowel diseases and cancer1. We used the Drosophila midgut2 to investigate this and discovered that during regeneration a subpopulation of cholinergic3 neurons triggers Ca2+ currents among intestinal epithelial cells, the enterocytes, to promote return to homeostasis. We found that down-regulation of the conserved cholinergic enzyme Acetylcholinesterase4 in the gut epithelium enables acetylcholine from specific TNF/Egr5-sensing cholinergic neurons to activate nicotinic receptors in innervated enterocytes. This activation triggers high Ca2+ that spreads in the epithelium through Inx2/Inx7 gap junctions6, promoting enterocyte maturation followed by reduction of proliferation and inflammation. Disrupting this process causes chronic injury consisting of ion imbalance, Yki/Yap activation7, cell death and increase of inflammatory cytokines reminiscent of inflammatory bowel diseases8. Altogether, the conserved cholinergic pathway facilitates epithelial Ca2+ currents that heal the intestinal epithelium. Our findings demonstrate nerve- and bioelectric9-dependent intestinal regeneration and advance our current understanding of how a tissue returns to homeostasis after injury.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.