Active Lungs & Breathing Diabetes, Hormones & Metabolism

Defining the role of lung macrophage metabolism during lung fibrosis

Funder Wellcome Charity-funded
Recipient organisation Imperial College London
Funding £1.8M
Period Dec 2022 — Nov 2029

In plain English

AI plain-English summary

Macrophages—the immune cells that normally clean up lung tissue after injury—are switching their internal fuel supply in ways that drive the scarring seen in idiopathic pulmonary fibrosis (IPF). IPF is a chronic, incurable disease in which the lungs become progressively stiff with excess scar tissue, eventually suffocating the patient. The fundamental problem is that the wound-healing process never turns off. This project targets a specific gap: no one knows exactly how the metabolic changes inside lung macrophages push them from repair into fibrosis. The researcher has already shown that these cells are metabolically rewired during disease and that the rewiring correlates with severity. If the work succeeds, it could reveal a new class of drug targets—ones that correct the macrophage’s fuel choice rather than simply dampening inflammation. Using animal models, human cells, and patient samples, the project will test whether blocking lipid metabolism in macrophages can halt or reverse fibrosis. This is primarily fundamental science: it aims to map the metabolic pathways that tip the balance between healthy repair and scarring. A deeper understanding of those pathways could eventually lead to therapies that stop IPF at its metabolic root, rather than just managing symptoms.

View original technical description
Tissue wound healing is a normal consequence of injury but if dysregulated, can lead to pathology, as seen in idiopathic pulmonary fibrosis (IPF). IPF is a chronic debilitating lung disease with no cure, characterized by deposition of excessive extracellular matrix in the lung parenchyma. Macrophages are key components of lung defence with central roles in resolution of inflammation and repair. My published and preliminary work indicates that pulmonary macrophages are metabolically rewired during fibrosis and furthermore, that these metabolic phenotypes are related to disease severity. I hypothesise that metabolic alterations underlie pulmonary macrophage profibrotic phenotypes and that targeting macrophage metabolism is a tractable therapeutic strategy. This project aims to answer the following key questions (Figure 1A); - What are the metabolic phenotype and nutrient dependencies of macrophage subsets in the fibrotic lung? - How does macrophage metabolism influence stromal phenotypes in the fibrotic lung? - Can targeting lipid metabolism in macrophages ameliorate lung fibrosis? Using innovative tools and therapeutics I will define the role of lung macrophage metabolism using robust animal models, primary human cells, and unique clinical cohorts. Together, these studies will delineate the pathways that define balance between health and disease, revealing novel approaches for therapeutic intervention.

View the original record at the funder ↗

Researchers

Adam Byrne (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

The functional role of macrophages in the progression and resolution of lung fibrosis.
The role of macrophage lipid metabolism in pulmonary fibrosis
Reprogramming alveolar macrophages in IPF
Investigating the role of TGFβ in the functional imprinting of pulmonary macrophages in health and disease
Investigation of the Pro-Fibrogenic Macrophage Populations Driving Pulmonary Fibrogenesis Using a Single Cell RNA Sequencing Approach

Original classification

Discovery Award

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