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

被引：1

作者：

Wang, Yinsheng ^{[1
,2
,3
,4
]}

Zhang, Xiaoyu ^{[5
,6
,7
]}

Liu, Shaorui ^{[2
,3
,4
]}

Gu, Zhijie ^{[5
,6
,7
,8
]}

Sun, Zijia ^{[2
,3
,4
]}

Zang, Yang ^{[2
,3
,4
]}

Huang, Xiaobao ^{[9
,12
]}

Wang, Yi ^{[5
,6
]}

Wang, Qiang ^{[10
]}

Lin, Qingxia ^{[10
]}

Liu, Ruichao ^{[5
,6
,7
,8
]}

Sun, Suhua ^{[5
,6
,7
,11
]}

Xu, Hongkai ^{[5
,6
,7
]}

Wang, Jiali ^{[5
,6
,7
,8
]}

Wu, Tao ^{[5
,6
,7
,8
]}

Wang, Yan ^{[2
,3
,4
]}

Li, Yu ^{[2
,3
,4
]}

Li, Hui ^{[2
,3
,4
]}

Tang, Zirun ^{[5
,6
,7
]}

Qu, Yifan ^{[5
,6
,7
]}

Wu, Li ^{[5
,6
,7
,8
]}

Hu, Xiaoyu ^{[5
,6
,7
,8
]}

Guo, Xiaohuan ^{[5
,6
,7
]}

Wang, Fang ^{[9
,13
]}

Zhou, Lei ^{[10
]}

He, Danyang ^{[2
]}

Qi, Hai ^{[5
,6
,7
,8
,11
,14
,15
,16
]}

Xu, Heping ^{[2
,3
,4
]}

Chu, Coco ^{[5
,6
,7
,8
,16
,17
]}

机构：

[1] Fudan Univ, Shanghai 200433, Peoples R China

[2] Westlake Lab Life Sci & Biomed, Hangzhou 310024, Zhejiang, Peoples R China

[3] Westlake Univ, Sch Med, Lab Syst Immunol, Hangzhou 310024, Zhejiang, Peoples R China

[4] Westlake Univ, Sch Life Sci, Key Lab Growth Regulat & Translat Res Zhejiang Pro, Hangzhou 310024, Peoples R China

[5] Tsinghua Univ, Inst Immunol, Beijing 100084, Peoples R China

[6] Tsinghua Univ, Sch Basic Med Sci, Beijing 100084, Peoples R China

[7] Tsinghua Univ, Beijing Key Lab Immunol Res Chron Dis, Beijing 100084, Peoples R China

[8] Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China

[9] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Dermatol, Guangzhou 510080, Peoples R China

[10] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Immune Therapy Inst, Shanghai 200127, Peoples R China

[11] Changping Lab, Beijing 102206, Peoples R China

[12] State Key Lab Membrane Biol, Beijing 100084, Peoples R China

[13] Guangdong Prov Key Lab Brain Funct & Dis, Guangzhou 510080, Peoples R China

[14] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China

[15] Tsinghua Univ, Beijing Frontier Res Ctr Biol Struct, Beijing 100084, Peoples R China

[16] Shanxi Med Univ, SXMU Tsinghua Collaborat Innovat Ctr Frontier Med, Taiyuan 030001, Shanxi Province, Peoples R China

[17] Capital Med Univ, Beijing Friendship Hosp, State Key Lab Digest Hlth, Beijing 100050, Peoples R China

来源：

IMMUNITY | 2025年 / 58卷 / 02期

基金：

国家重点研发计划; 中国国家自然科学基金;

关键词：

INNATE LYMPHOID-CELLS; PRIMARY AFFERENT NEURONS; GENE-RELATED PEPTIDE; NERVOUS-SYSTEM; GUT; BRAIN; DELETION; IMMUNITY; CIRCUITS; PROMOTES;

D O I：

10.1016/j.immuni.2025.01.004

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 b-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 b-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.

引用

页码：465 / 480.e8

页数：25