Interstitial lung diseases (ILD) is one of the primary causes of death worldwide. Idiopathic ILD is largely considered untreatable due to the lacking response to anti-inflammatory drugs such as corticosteroids and/or conventional DMARDs. Survival is poor with 2-3 years of initial diagnosis.
Our project challenges the assumption that ILD is a non-immunogenic disease. The lacking response to T-/B-cell targeted conventional immunosuppressive agents does not preclude underlying (innate) immune mechanisms that finally result in pulmonary fibrosis.
We hypothesize that multifactorial and probably varying triggers (including infections or exposure to chemical or physical stressors e.g. drugs, acid aspiration, smoking, radiation, trauma), cause either alveolar epithelial or endothelial cell damage, with subsequent local inflammation driven by neutrophils and macrophages. Multiple hits on the background of a genetic susceptibility might then lead to chronic activation of resident structural cells, with dysregulation of tissue repair and resolution resulting in pulmonary fibrosis.
Using a variety of pathophysiological mouse models of ILD, we will evaluate key effector cells and key pathways in different pathophysiologic disease stages, including tissue injury, inflammation, fibrosis, repair and resolution, in order to identify potential therapeutic targets.
Source: Meneghin A, Hogaboam CM. J. Clin. Invest. 117:530–538 (2007). doi:10.1172/JCI30595