神经上皮回路促进感觉收敛和肠道免疫，这一成果由威尔康奈尔医学院David Artis研究组经过不懈努力而取得。相关论文于2026年1月7日发表在《自然》杂志上。

在这里，研究组发现TRPV1+痛觉伤害感受器协同化学感觉上皮簇状细胞启动一系列组织反应，驱动类型2炎症。化学发生沉默或化学消融TRPV1+伤害感受器导致肠簇状细胞显著减少和抗蠕虫型缺陷2免疫。相比之下，TRPV1+伤害感受器的化学激活导致CGRP+神经纤维的重塑，CGRP表达显著增加，簇状细胞积聚增强和保护性抗蠕虫型2免疫。利用空间转录组学和单细胞RNA测序分析，研究小组发现伤害受体的激活促进了上皮祖细胞的快速增殖和分化。从机制上讲，肠上皮细胞和簇状细胞内在表达CGRP受体亚基是簇状细胞反应和分型所必需的。对寄生虫感染有免疫力。总之，这些结果确定了神经元-上皮簇状细胞回路的感觉收敛是类型的关键上游决定因素。2免疫和组织适应。

据了解，类型2屏障表面的炎症是一种进化上保守的反应，可促进对寄生虫、过敏性炎症和组织修复的免疫。上皮细胞直接感知环境触发触发触发型2炎症，以及来自神经元的信号可以调节免疫反应。然而，来自上皮细胞、神经元细胞和免疫细胞的各种感觉输入是如何协调和整合的仍不清楚。

附：英文原文

Title: Neuro-epithelial circuits promote sensory convergence and intestinal immunity

Author: Zhang, Wen, Emanuel, Elizabeth R., Yano, Hiroshi, Uddin, Jazib, Gaudino, Stephen, Xie, Zili, Ichise, Hiroshi, Wang, Zhen, Cowan, Maureen N., Lyu, Mengze, Hou, Xiaoxiao, Zeng, Peng, Hu, Elin, Ribeiro de Godoy, Victoria, Grier, Alex, Estep, Nina, Ishibashi, Julien R., Anover-Sombke, Stephanie, Skene, Peter J., Mayassi, Toufic, Xavier, Ramnik J., Germain, Ronald N., Globig, Anna-Maria, Heeg, Maximilian, Goldrath, Ananda W., Kim, Brian S., Hu, Hongzhen, Artis, David

Issue&Volume: 2026-01-07

Abstract: Type2 inflammation at barrier surfaces is an evolutionarily conserved response that promotes immunity to helminth parasites, allergic inflammation and tissue repair1,2,3,4. Direct sensing of environmental triggers by epithelial cells initiates type2 inflammation, and signals derived from neurons can modulate immune responses5,6,7,8. However, how diverse sensory inputs from epithelial, neuronal and immune cells are coordinated and integrated remains unclear. Here we identify that TRPV1+ pain-sensing nociceptors co-opt chemosensory epithelial tuft cells to initiate a cascade of tissue responses that drive type2 inflammation. Chemogenetic silencing or chemical ablation of TRPV1+ nociceptors results in a significant reduction in intestinal tuft cells and defective anti-helminth type2 immunity. By contrast, chemogenetic activation of TRPV1+ nociceptors leads to remodelling of CGRP+ nerve fibres, significantly increased CGRP expression, enhanced tuft cell accumulation and protective anti-helminth type2 immunity. Using spatial transcriptomic and single-cell RNA sequencing analyses, we reveal that nociceptor activation promotes rapid epithelial progenitor cell proliferation and differentiation. Mechanistically, intestinal epithelial cell-intrinsic and tuft cell-intrinsic expression of CGRP receptor subunits are required for tuft cell responses and type2 immunity to helminth infection. Together, these results identify sensory convergence of a neuronal–epithelial tuft cell circuit as a critical upstream determinant of type2 immunity and tissue adaptation.

DOI: 10.1038/s41586-025-09921-z

Source: https://www.nature.com/articles/s41586-025-09921-z