Henrique Veiga-Fernandes研究团队近日取得一项新成果。经过不懈努力，他们的最新研究揭示了神经上皮VIP-VIPR1相互作用差异控制肠道1型和2型免疫。2025年11月24日出版的《自然—免疫学》杂志发表了这项成果。

该课题组人员确定了神经上皮相互作用对肠道1型和2型免疫的差异控制。肠道上皮细胞表达血管活性肠肽（VIP）受体1 (VIPR1)，肠道VIPergic神经元的化学发生调节导致上皮源性细胞因子的改变。Vipr1的上皮内在缺失导致1型免疫功能减弱，包括1型警报和上皮内淋巴细胞减少。相反，上皮Vipr1缺失导致2型免疫增强，包括2型警报器、簇状细胞和激活的2组先天淋巴样细胞增加。神经上皮VIP-VIPR1相互作用的破坏导致对侵袭性细菌感染的易感性增加，这与对寄生虫感染的抵抗力增强形成对比。他们的工作确定了控制1型和2型免疫的多组织轴，破译了神经上皮相互作用如何独特地设置肠道免疫程序。

研究人员表示，神经系统和免疫系统共同调节粘膜屏障的完整性。然而，肠神经元是否建立神经上皮相互作用来协调免疫仍然是未知的。

附：英文原文

Title: Neuroepithelial VIP–VIPR1 interactions differentially control enteric type 1 and type 2 immunity

Author: Pirzgalska, Roksana M., Henriques-Alves, Beatriz, Raposo, Bruno, de Sousa, Eric, Torres, Jlio, Ryu, Jaechan, Godinho-Silva, Cristina, Rendas, Miguel, Pereira, Madalena, Godinho, Ins, Ribeiro, Hlder, Correia, Vasco, Jakob, Manuel O., Forster, Patrycja M., Wilhelm, Christoph, Klose, Christoph S. N., Rio-Tinto, Ricardo, Link, Verena M., Carvalho, Tnia, Minutti, Carlos M., Ferreira, Manuela, Veiga-Fernandes, Henrique

Issue&Volume: 2025-11-24

Abstract: The nervous and immune systems cooperate to regulate mucosal barrier integrity. Nevertheless, whether enteric neurons establish neuroepithelial interactions to coordinate immunity remains elusive. Here, we identified neuroepithelial interactions that differentially control intestinal type 1 and type 2 immunity. Gut epithelial cells expressed vasoactive intestinal peptide (VIP) receptor 1 (VIPR1), and chemogenetic modulation of enteric VIPergic neurons led to altered epithelial-derived cytokines. Epithelial-intrinsic deletion of Vipr1 resulted in diminished type 1 immunity, including reduced type 1 alarmins and intraepithelial lymphocytes. In contrast, epithelial Vipr1 deficiency led to enhanced type 2 immunity, comprising increased type 2 alarmins, tuft cells and activated group 2 innate lymphoid cells. Disruption of neuroepithelial VIP–VIPR1 interactions resulted in increased susceptibility to invasive bacterial infection, which contrasted with enhanced resistance to parasite infection. Our work identifies a multi-tissue axis that controls type 1 and type 2 immunity, deciphering how neuroepithelial interactions distinctively set gut immunity programs.

DOI: 10.1038/s41590-025-02326-0

Source: https://www.nature.com/articles/s41590-025-02326-0