How changes in lung tissue structure drive fibrotic lung disease
In this project, academic partners from the University of Groningen will collaborate with partners from Boehringer Ingelheim to understand the cues for the derailed activity of specific immune cells, so-called macrophages, in the lung disease pulmonary fibrosis. These cells contribute to the disease process in pulmonary fibrosis, which results in increased stiffness of lung tissues leading to difficulties with breathing. We hypothesize that the tissue micro-environment of the macrophages, which includes structural protein fibers and the cells that produce these, stromal (stem) cells, are responsible for the abnormal repair of lung tissue in fibrosis. These alterations in the tissue then act in a self-amplifying manner, driving macrophages to promote the fibrotic response.
Lung fibrosis is a rare, debilitating disease that affects around 3000 people in the Netherlands. It has a high impact on quality of life of patients and a mortality rate worse than most cancers. Lung fibrosis cannot be cured and there are very few drugs to treat this disease, creating an urgent need for novel therapeutic strategies.
In order to find new therapeutic strategies, we need to obtain more insight into the disease mechanisms. In our project, we will investigate whether the abnormal activity of stromal (stem) cells and/or the composition of the lung tissue and the abundance of structural proteins in fibrotic lungs alter the behavior of macrophages. We will use cells and tissue from the lungs of healthy controls and lung fibrosis patients and combine these in novel 3-dimensional culture models to study the effects on macrophages and determine which components are crucial for inducing the pathological changes. Through comparing responses in diseased and non-diseased microenvironments we will understand which factors contribute to the altered behavior of macrophages. With this knowledge we expect to identify novel therapeutic targets for pulmonary fibrosis, which we will validate in our model system.
Dissemination has occurred throughout the project to the scientific and clinical research community through presentations at field specific meetings including the American Thoracic Society Annual Scientific Meeting, Tissue Engineering and Regenerative Medicine International Society (TERMIS) World Congress, European Respiratory Society Research Seminar: Innovative 3D Models, Dutch Society for Matrix Biology, Extracellular Matrix in Pharmacology Congress, International Colloquium for Airway and Lung Fibrosis. Through a presentation at the Dutch Lung Congress the information about the project was communicated to translational respiratory researchers, clinicians and patients with lung diseases, their caregivers and their representative organisation.
