Dog allergen-induced asthma in mice: a relevant model of T2low severe asthma with airway remodelling

• Published in: Inflammation research Vol. 74; no. 1; p. 52
• Main Authors: Margelidon-Cozzolino, Victor, Balsamelli, Joanne, Carrard, Julie, Ait Yahia, Saliha, Gevaert, Marie-Hélène, Demoulin-Alexikova, Silvia, Pichavant, Muriel, Tsicopoulos, Anne, Chenivesse, Cécile, Lejeune, Stéphanie, de Nadai, Patricia
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.12.2025; Springer Nature B.V
• Subjects: Allergens; Allergology; Animal models; Asthma; Biomedical and Life Sciences; Biomedicine; Bronchus; Dermatology; Dexamethasone; Dogs; Fibrosis; Helper cells; Hypertrophy; Immunology; Inflammation; Lavage; Leukocytes (neutrophilic); Lymphocytes T; Methacholine; Neurology; Original Research Paper; Pharmacology/Toxicology; Respiratory tract diseases; Rheumatology; Smooth muscle; Steroid hormones; Steroids; Therapeutic targets; Dog allergen; Airway remodelling; Th17 inflammation; Neutrophils; Asthma; Steroids
• ISSN: 1023-3830; 1420-908X; 1420-908X
• DOI: 10.1007/s00011-025-02004-9

Objective and design Airway remodelling (AR) is a disabling phenomenon in patients with severe asthma, yet suitable models are lacking. We previously developed a dog allergen-induced murine asthma model characterized by T2 low Th17-driven neutrophilic airway inflammation and AR. To assess its relevance to human AR associated with T2 low severe asthma, a condition characterised by poor response to inhaled steroids, we tested the steroid sensitivity of the key features of this model. Material Asthma was induced in C57BL/6 J mice by intranasal sensitization, followed by a three-week challenge with dog allergen. Treatment : Daily intraperitoneal 1 mg kg −1 dexamethasone was administrated during the last week of challenge. Methods : We measured airway resistances in response to methacholine, cellular inflammation in bronchoalveolar lavage, lung cytokines, and quantified AR features, in response to dexamethasone. Results Dexamethasone-treated mice showed persistent airway hyperresponsiveness, neutrophilic inflammation, and Il17 a overexpression, whereas Il22 expression was abrogated. Pathological AR features, including mucus hyperproduction, subepithelial fibrosis and smooth muscle hypertrophy were not eliminated by dexamethasone. Conclusions Our dog allergen-induced murine model of asthma mirrors the steroid-insensitive traits of human severe T2 low asthma with AR, making it a relevant tool for identifying novel therapeutic targets in this orphan asthma subset.