A76-27 A Novel Preclinical Mouse Model of Neutrophilic Asthma: Advancing Mechanistic Studies and Therapeutic Development

Rationale

Neutrophilic asthma is a rare and difficult-to-treat asthma subtype, characterized by neutrophilic inflammation and poor response to conventional therapies. The lack of reliable preclinical models complicates the evaluation of potential therapeutics, hindering the translation of experimental findings into effective clinical treatments. This gap limits the development of targeted therapies for neutrophilic asthma.

Methods

Neutrophilic asthma was induced in B-hTSLP/hTSLPR/IL-7R transgenic and wild-type (WT) mice using an OVA/CFA stimulation following OVA/LPS challenge. Tezepelumab, a monoclonal antibody targeting neutrophilic asthma in clinical trial, was administered to validate the model. Airway hyperresponsiveness, inflammatory cell infiltration in bronchi alveolar lavage fluid (BALF), and lung pathological changes were assessed to characterize airway inflammation and evaluate this model.

Results

In hTSLP/hTSLPR/IL-7R transgenic and WT mice, significant changes in airway hyperreactivity and inflammatory cell infiltration were observed in the vehicle group compared to the sham group, with neutrophils predominating in BALF. Increased airway mucus secretion and goblet cell hyperplasia were also observed in lung tissue. Tezepelumab treatment significantly reduced the mucus secretion and goblet cell proliferation. In addition,Following Tezepelumab administration, airway hyperreactivity was improved, with a significant reduction in inflammatory cell infiltration, particularly neutrophils as well as the levels of IL-17 and TNF-α in BALF and serum, were markedly lower than in the vehicle group.

Conclusions

This study identify a novel mouse a novel mouse model of neutrophilic asthma, with Tezepelumab. This model could serve as a promising reliable preclinical model to facilitate the translation of experimental findings into clinically applicable treatments, potentially advancing the development of targeted therapies for neutrophilic asthma.

This abstract is funded by: WuXi AppTec