Bi-directional communication between intrinsic enteric neurons and ILC2s inhibits host defense against helminth infection

IF 25.5 1区医学 Q1 IMMUNOLOGY

Immunity Pub Date : 2025-01-30 DOI:10.1016/j.immuni.2025.01.004

Yinsheng Wang, Xiaoyu Zhang, Shaorui Liu, Zhijie Gu, Zijia Sun, Yang Zang, Xiaobao Huang, Yi Wang, Qiang Wang, Qingxia Lin, Ruichao Liu, Suhua Sun, Hongkai Xu, Jiali Wang, Tao Wu, Yan Wang, Yu Li, Hui Li, Zirun Tang, Yifan Qu, Coco Chu

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Abstract

Emerging studies reveal that neurotransmitters and neuropeptides play critical roles in regulating anti-helminth immune responses, hinting at the potential of intrinsic enteric neurons (iENs) in orchestrating intestinal immunity. Whether and how iENs are activated during infection and the potential neuroimmune interactions involved remain poorly defined. Here, we found that helminth infection activated a subset of iENs. Single-nucleus RNA sequencing (snRNA-seq) of iENs revealed alterations in the transcriptional profile of interleukin (IL)-13R⁺ intrinsic primary afferent neurons (IPANs), including the upregulation of the neuropeptide β-calcitonin gene-related peptide (CGRP). Using genetic mouse models and engineered viral tools, we demonstrated that group 2 innate lymphoid cell (ILC2)-derived IL-13 was required to activate iENs via the IL-13R, leading to iEN production of β-CGRP, which subsequently inhibited ILC2 responses and anti-helminth immunity. Together, these results reveal a previously unrecognized bi-directional neuroimmune crosstalk in the intestine between a subset of iENs and ILC2s, which influences pathogen clearance.

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来源期刊

Immunity 医学-免疫学

CiteScore

49.40

自引率

2.20%

发文量

205

审稿时长

6 months

期刊介绍： Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.