The Journal of asthma : official journal of the Association for the Care of Asthma · 2026
TRPV1+ nociceptor neurons promote airway neurogenic inflammation in CVA via substance P-dependent macrophage M1 polarization.
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Zhang Jinjun, Song Ying, Mi Xuancheng, Hu Ying
Аннотация
BACKGROUND: Cough variant asthma (CVA) is characterized by chronic cough and airway hypersensitivity, in which transient receptor potential vanilloid 1 (TRPV1)-mediated neurogenic inflammation plays a critical role.
OBJECTIVE: This study aimed to investigate whether chemical ablation of TRPV1-expressing nociceptor neurons alleviates CVA symptoms and to explore their involvement in airway inflammation via substance P (SP)-dependent macrophage polarization.
METHODS: A murine CVA model was induced by OVA. TRPV1+ nociceptor neurons were ablated intrathecally using resiniferatoxin (RTX). We assessed cough response, lung inflammation (BALF cytometry, ELISA, histology), fibrosis (Masson/Sirius Red), and neurogenic mediators (SP/CGRP). In vitro, a dorsal root ganglion (DRG) neuron-RAW264.7 macrophage co-culture system, combined with TRPV1 knockdown and NK-1R blockade, was used to define the TRPV1-SP-macrophage polarization axis.
RESULTS: In an OVA-induced CVA mouse model, chemical ablation of TRPV1+ DRG neurons with RTX significantly reduced cough frequency, attenuated pulmonary inflammation and fibrosis, and suppressed neurogenic inflammatory factors including SP and CGRP. In vitro, TRPV1 activation in primary DRG neurons promoted SP release, which via neurokinin-1 receptor drove macrophages toward an M1 phenotype, upregulating pro-inflammatory markers. Inhibition of SP signaling blocked this polarization.
CONCLUSIONS: Our results reveal a novel TRPV1-SP-macrophage M1 axis in CVA pathogenesis, suggesting that targeting this neuroimmune pathway may offer a therapeutic strategy for CVA.
OBJECTIVE: This study aimed to investigate whether chemical ablation of TRPV1-expressing nociceptor neurons alleviates CVA symptoms and to explore their involvement in airway inflammation via substance P (SP)-dependent macrophage polarization.
METHODS: A murine CVA model was induced by OVA. TRPV1+ nociceptor neurons were ablated intrathecally using resiniferatoxin (RTX). We assessed cough response, lung inflammation (BALF cytometry, ELISA, histology), fibrosis (Masson/Sirius Red), and neurogenic mediators (SP/CGRP). In vitro, a dorsal root ganglion (DRG) neuron-RAW264.7 macrophage co-culture system, combined with TRPV1 knockdown and NK-1R blockade, was used to define the TRPV1-SP-macrophage polarization axis.
RESULTS: In an OVA-induced CVA mouse model, chemical ablation of TRPV1+ DRG neurons with RTX significantly reduced cough frequency, attenuated pulmonary inflammation and fibrosis, and suppressed neurogenic inflammatory factors including SP and CGRP. In vitro, TRPV1 activation in primary DRG neurons promoted SP release, which via neurokinin-1 receptor drove macrophages toward an M1 phenotype, upregulating pro-inflammatory markers. Inhibition of SP signaling blocked this polarization.
CONCLUSIONS: Our results reveal a novel TRPV1-SP-macrophage M1 axis in CVA pathogenesis, suggesting that targeting this neuroimmune pathway may offer a therapeutic strategy for CVA.