Mij
Senior Member (Voting Rights)
Researchers from UCD School of Medicine and UCD Conway Institute have collaborated with Imperial College London and King’s College London on their recently published paper in Allergy, titled, ‘Protective Role for Itaconate During Inhaled Allergen Challenge’. The research was supported by Asthma + Lung UK and Wellcome Trust.
The project was a team effort led by Dr Gesa Albers. UCD School of Medicine’s Professor Adam Byrne was a supervisor. The team reported:
Reduced itaconate in the airways of allergen-challenged people with mild asthma, but no change in itaconate levels when comparing across asthma severities
Using preclinical models, they show that inhaled itaconate plays a protective role, restraining excessive inflammation.
This points to immunometabolism as a promising route for new asthma therapeutics.
ABSTRACT
Background
Asthma is a chronic, heterogeneous disease characterised by airway remodelling, inflammation, and mucus production. Airway macrophages' functions are underpinned by changes in cellular metabolism. The TCA cycle-derived metabolite itaconic acid (whose synthesis is mediated by aconitate decarboxylase) is a master regulator of macrophage function; however, its role during inhaled allergen challenge is not clear. The objective of this study was to define the role of itaconate during inhaled allergen challenge.
Methods
Sputum metabolite levels were measured in participants with mild allergic asthma undergoing allergen inhalation challenge, and in a second cohort, baseline levels in mild, moderate, and severe asthmatics. Airway inflammation, lung function, and bronchoalveolar lavage metabolite levels were assessed in wild-type and aconitate decarboxylase-deficient mice, or in mice treated with inhaled itaconate.
Results
Allergen inhalation in mild asthmatics led to a significant reduction in sputum itaconate. We found no difference in baseline sputum itaconate levels when comparing healthy controls to mild, moderate, or severe asthmatics. Continuous exposure to aeroallergen in wild type and aconitate decarboxylase-deficient mice showed no change in disease phenotype after 48 h, 1, 3, or 5 weeks of allergen exposure. Treatment of house dust mite-exposed mice with inhaled itaconate reduced airway inflammation.
Conclusion
Levels of itaconate are altered after allergen challenge in mild asthmatics and in murine models of disease. Itaconate deficiency did not alter house dust mite-induced pathology at any of the timepoints tested; however, inhaled itaconate ameliorated inflammatory responses to inhaled allergen.
Paper here
The project was a team effort led by Dr Gesa Albers. UCD School of Medicine’s Professor Adam Byrne was a supervisor. The team reported:
Reduced itaconate in the airways of allergen-challenged people with mild asthma, but no change in itaconate levels when comparing across asthma severities
Using preclinical models, they show that inhaled itaconate plays a protective role, restraining excessive inflammation.
This points to immunometabolism as a promising route for new asthma therapeutics.
ABSTRACT
Background
Asthma is a chronic, heterogeneous disease characterised by airway remodelling, inflammation, and mucus production. Airway macrophages' functions are underpinned by changes in cellular metabolism. The TCA cycle-derived metabolite itaconic acid (whose synthesis is mediated by aconitate decarboxylase) is a master regulator of macrophage function; however, its role during inhaled allergen challenge is not clear. The objective of this study was to define the role of itaconate during inhaled allergen challenge.
Methods
Sputum metabolite levels were measured in participants with mild allergic asthma undergoing allergen inhalation challenge, and in a second cohort, baseline levels in mild, moderate, and severe asthmatics. Airway inflammation, lung function, and bronchoalveolar lavage metabolite levels were assessed in wild-type and aconitate decarboxylase-deficient mice, or in mice treated with inhaled itaconate.
Results
Allergen inhalation in mild asthmatics led to a significant reduction in sputum itaconate. We found no difference in baseline sputum itaconate levels when comparing healthy controls to mild, moderate, or severe asthmatics. Continuous exposure to aeroallergen in wild type and aconitate decarboxylase-deficient mice showed no change in disease phenotype after 48 h, 1, 3, or 5 weeks of allergen exposure. Treatment of house dust mite-exposed mice with inhaled itaconate reduced airway inflammation.
Conclusion
Levels of itaconate are altered after allergen challenge in mild asthmatics and in murine models of disease. Itaconate deficiency did not alter house dust mite-induced pathology at any of the timepoints tested; however, inhaled itaconate ameliorated inflammatory responses to inhaled allergen.
Paper here