A key function of the pulmonary tract is the ability to maintain immune tolerance despite continuous exposure to inhaled antigens. In particular, pulmonary macrophage populations are key sentinels of lung homeostasis. Airway macrophages (AMs) reside in the airways and maintain immune tolerance despite continuous exposure to inhaled antigens. My work aims to explore key molecular mechanisms and pathways that dictate airway macrophage responses during chronic lung disease. In particular, I focus on the role of AMs in asthma and idiopathic pulmonary fibrosis (IPF), a devastating disease with limited therapeutic options.
How does airway macrophage glycolytic reprogramming contribute to fibrotic lung disease?
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 expression of glucose transport molecules; however, whether AM-glycolytic programming contributes to the pathogenesis of lung fibrosis remains unknown. This project aims to determine AM metabolic signatures in the fibrotic lung and determine the effect of modulating these pathways.