Selective PAR2 Inhibition Attenuates HDM-Induced Th1/Th2 Responses in Human Epithelial and Murine Models of Allergic Rhinitis and Asthma

Miran Kang; Yohan Seo; Ju Hee Seo; Yeonsu Jeong; Hyejin Jeon; Su-Myeong Jang; Chang-Hoon Kim; Wan Namkung; Hyung-Ju Cho

doi:Background: Allergic rhinitis (AR) and asthma are involved in complex interactions between Th1 and Th2 inflammatory pathways. House dust mite (HDM) activates protease-activated receptor 2 (PAR2) to trigger inflammatory responses, but current treatments often provide inadequate control.

Objective: This study aimed to investigate the effects of selective PAR2 inhibition on Th1 and Th2 responses in human nasal epithelial (HNE) cells and murine models of AR and asthma.

Methods: We examined the effects of selective PAR2 inhibition using primary HNE cells and HDM-induced mouse models (PAR2-wild-type [PAR2-wt] and knockout [PAR2-ko]). Analyses included inflammatory signaling pathways, cytokine profiles, airway responses, histopathology, and transcriptomics.

Results: In HNE cells, PAR2 inhibition suppressed Th2 (interleukin [IL]-33, TSLP) and Th1 (TNF-α, IL-6) inflammatory cytokines while inhibiting calcium mobilization and ERK/NF-κB signaling cascades. In PAR2-wt mice, treatment with the PAR2 inhibitor reduced HDM-specific Immunoglobulin E (IgE), airway hyperresponsiveness, and allergic inflammation in both nasal and bronchial tissues, matching the anti-inflammatory profile of PAR2-ko mice. Bulk RNA sequencing confirmed comprehensive suppression of inflammatory gene expression.

Conclusions: Selective PAR2 inhibition effectively attenuates HDM-induced allergic inflammation by modulation of Th1 and Th2 pathways in human airway epithelium and murine models. We suggest that PAR2 can be a possible target for AR and asthma.

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Selective PAR2 Inhibition Attenuates HDM-Induced Th1/Th2 Responses in Human Epithelial and Murine Models of Allergic Rhinitis and Asthma

Authors: Miran Kang ; Yohan Seo ; Ju Hee Seo ; Yeonsu Jeong ; Hyejin Jeon ; Su-Myeong Jang ; Chang-Hoon Kim ; Wan Namkung ; Hyung-Ju Cho

Citation: INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY, Vol.11 : e23623, 2025-07

Journal Title: INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY

ISSN: 2042-6976

Issue Date: 2025-07

MeSH: 1

Abstract: Th1/Th2 responses; allergic airway inflammation; protease‐activated receptor 2; punicalagin; rhinitis and asthma

Article Number: 10.1002/alr.23623

DOI: Background: Allergic rhinitis (AR) and asthma are involved in complex interactions between Th1 and Th2 inflammatory pathways. House dust mite (HDM) activates protease-activated receptor 2 (PAR2) to trigger inflammatory responses, but current treatments often provide inadequate control. Objective: This study aimed to investigate the effects of selective PAR2 inhibition on Th1 and Th2 responses in human nasal epithelial (HNE) cells and murine models of AR and asthma. Methods: We examined the effects of selective PAR2 inhibition using primary HNE cells and HDM-induced mouse models (PAR2-wild-type [PAR2-wt] and knockout [PAR2-ko]). Analyses included inflammatory signaling pathways, cytokine profiles, airway responses, histopathology, and transcriptomics. Results: In HNE cells, PAR2 inhibition suppressed Th2 (interleukin [IL]-33, TSLP) and Th1 (TNF-α, IL-6) inflammatory cytokines while inhibiting calcium mobilization and ERK/NF-κB signaling cascades. In PAR2-wt mice, treatment with the PAR2 inhibitor reduced HDM-specific Immunoglobulin E (IgE), airway hyperresponsiveness, and allergic inflammation in both nasal and bronchial tissues, matching the anti-inflammatory profile of PAR2-ko mice. Bulk RNA sequencing confirmed comprehensive suppression of inflammatory gene expression. Conclusions: Selective PAR2 inhibition effectively attenuates HDM-induced allergic inflammation by modulation of Th1 and Th2 pathways in human airway epithelium and murine models. We suggest that PAR2 can be a possible target for AR and asthma.

Appears in Collections:: 1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers

Yonsei Authors: Kim, Chang Hoon(김창훈) https://orcid.org/0000-0003-1238-6396
Cho, Hyung Ju(조형주) https://orcid.org/0000-0002-2851-3225

URI: https://ir.ymlib.yonsei.ac.kr/handle/22282913/207428

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