Targeting alveolar macrophage self-renewal to maintain lung homeostasis and prevent chronic inflammatory lung disease
Principal Investigator
Scientific interest within the context of the graduate college
Active maintenance of tissue health requires maintenance of tissue-resident macrophages that perform homeostatic functions. Loss of tissue-resident macrophages reduces the ability of tissues to maintain homeostasis or to return to homeostasis after inflammation. We propose that exploring the mechanisms that maintain tissue-resident macrophages will allow us to identify molecular targets that promote tissue health and to achieve deeper remission after treatment of chronic inflammatory diseases.
Project description
Alveolar macrophages play an active role in maintaining lung homeostasis by clearing apoptotic cells, catabolizing surfactant produced by alveolar epithelial cells and mediating antimicrobial immunity. Loss of alveolar macrophage function results in inability to maintain lung homeostasis, susceptibility to infection and exacerbated inflammatory responses. Despite their importance, the mechanisms that actively maintain alveolar macrophages and thus secure lung homeostasis are largely unknown.
The project will explore the mechanisms that maintain alveolar macrophages. To do this, we will employ transgenic mouse models that allow targeting alveolar macrophages in two different stages of their development. Alveolar macrophages will be isolated using bronchoalveolar lavage and their proliferation capacity, transcriptional program, metabolism and ability to clear apoptotic cells will be studied ex vivo.
Overall, this line of work aims to uncover essential pathways that promote alveolar macrophage maintenance and may be targeted to prevent lung injury and pulmonary fibrosis in patients with autoimmunity.