How does airway macrophage glycolytic reprogramming contribute to fibrotic lung disease? (360G-Wellcome-205949_Z_17_Z)
Idiopathic pulmonary fibrosis (IPF) is the most common form of interstitial lung disease and is associated with high mortality. IPF therapies are limited and there is a significant need to understand the mechanisms involved. Airway macrophages (AMs) are the most abundant immune-cell in the IPF lung. Recent work demonstrated that IPF-AMs are characterised by high expession of glucose transport molecules; however, whether AM-glycolytic programming contributes to the pathogenesis of lung fibrosis remains unknown. My preliminary data indicates that IPF-AMs have a unique metabolic phenotype, characterised by reduced succinate and elevated Irg1 expression, a negative regulator of the citric acid cycle via itaconic acid. I hypothesise that AM glycolytic reprogramming contributes to the pathogenesis of lung fibrosis and manipulation of AM metabolism via itaconic acid, can ameliorate the disease. First, I will determine AM metabolic signatures in the fibrotic lung by metabolic assays in IPF-AMs and murine models. Second, I will assess Irg1 and itaconic acid levels in patient BAL/lung biopsies. Additionally, I will utilize siRNA knockdown in IPF-AMs and in parallel, Irg1-/- mice. This work will provide proof of principle for development of therapies which correct AM-metabolic dysregulation during IPF, paving the way for future grant applications and clinical studies.
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Grant Details
Amount Awarded | 96063 |
Applicant Surname | Byrne |
Approval Committee | Science Seeds Advisory Panel |
Award Date | 2016-11-29T00:00:00+00:00 |
Financial Year | 2016/17 |
Grant Programme: Title | Seed Award in Science |
Internal ID | 205949/Z/17/Z |
Lead Applicant | Dr Adam Byrne |
Partnership Value | 96063 |
Planned Dates: End Date | 2019-01-09T00:00:00+00:00 |
Planned Dates: Start Date | 2017-01-09T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Greater London |