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Updated: Aug 30, 2026

Identification and Characterization of Immunogenic RNA Species in HDM Allergens that Modulate Eosinophilic Lung Inflammation
Published on: May 30, 2020
Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling
Jill R Johnson1, Ryan E Wiley, Ramzi Fattouh
1Department of Pathology and Molecular Medicine, Center for Gene Therapeutics, Millennium Pharmaceuticals, Cambridge, Massachusetts, USA.
Abstract:
It is now fully appreciated that asthma is a disease of a chronic nature resulting from intermittent or continued aeroallergen exposure leading to airway inflammation. To investigate responses to continuous antigen exposure, mice were exposed to either house dust mite extract (HDM) or ovalbumin intranasally for five consecutive days, followed by 2 days of rest, for up to seven consecutive weeks. Continuous exposure to HDM, unlike ovalbumin, elicited severe and persistent eosinophilic airway inflammation. Flow cytometric analysis demonstrated an accumulation of CD4+ lymphocytes in the lung with elevated expression of inducible costimulator a marker of T cell activation, and of T1/ST2, a marker of helper T Type 2 effector cells. We also detected increased and sustained production of helper T cell Type 2-associated cytokines by splenocytes of HDM-exposed mice on in vitro HDM recall. Histologic analysis of the lung showed evidence of airway remodeling in mice exposed to HDM, with goblet cell hyperplasia, collagen deposition, and peribronchial accumulation of contractile tissue. In addition, HDM-exposed mice demonstrated severe airway hyperreactivity to methacholine. Finally, these responses were studied for up to 9 weeks after cessation of HDM exposure. We observed that whereas airway inflammation resolved fully, the remodeling changes did not resolve and airway hyperreactivity resolved only partly.
Insights
Continuous exposure to house dust mite extract (HDM) causes severe asthma-like symptoms in mice, including airway inflammation and remodeling. While inflammation resolves after exposure stops, airway hyperreactivity and remodeling persist, indicating long-term effects.
Area of Science:
- Immunology
- Pulmonology
- Allergy Research
Background:
- Asthma is a chronic airway inflammatory disease triggered by aeroallergen exposure.
- Understanding responses to continuous antigen exposure is crucial for asthma management.
Purpose of the Study:
- To investigate the effects of continuous house dust mite (HDM) or ovalbumin exposure on airway inflammation, remodeling, and hyperreactivity in mice.
- To assess the persistence of these changes after exposure cessation.
Main Methods:
- Mice were exposed intranasally to HDM or ovalbumin for five days weekly for up to seven weeks.
- Flow cytometry, cytokine analysis, histology, and methacholine challenge were used to assess airway responses.
- Responses were monitored up to nine weeks after HDM exposure cessation.
Main Results:
- Continuous HDM exposure, unlike ovalbumin, induced severe, persistent eosinophilic airway inflammation.
- HDM exposure led to T cell activation (CD4+ lymphocytes, inducible costimulator, T1/ST2) and elevated Th2 cytokines.
- Airway remodeling (goblet cell hyperplasia, collagen deposition) and severe airway hyperreactivity were observed in HDM-exposed mice.
- Post-exposure, airway inflammation resolved, but remodeling persisted, and hyperreactivity only partly resolved.
Conclusions:
- Continuous HDM exposure triggers significant and lasting asthma-like pathology in mice.
- Airway remodeling and hyperreactivity demonstrate incomplete resolution after antigen exposure ceases, highlighting the chronic nature of HDM-induced asthma.
- These findings underscore the importance of managing chronic allergen exposure in asthma.
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