Project Summary Lung disease is one of the leading causes of death in the world today, with chronic obstructive pulmonary disease (COPD) being the third leading cause of mortality worldwide. In such diseases, airway and alveolar functions are compromised; injuries in one region of the lung may affect and/or cause ensuing damage to other regions. We will use the naphthalene injury model in mice to study alveolar epithelial response to acute airway injury. The Kim Lab recently found that alveolar type 2 (AT2) cells proliferate in response to naphthalene injury. The immune system contributes to tissue regeneration post-injury and may facilitate local cell-cell interactions and tissue-wide responses. This project will determine if alveolar macrophages are responsible for the proliferative AT2 response after club cell injury. First, the extent of airway cell injury after macrophage depletion followed by naphthalene treatment will be examined by immunostaining analysis. Second, the proliferation and differentiation response of AT2 cells after macrophage depletion and naphthalene will be determined. This Diversity Supplement will support the scientific and career development of a research assistant. Importantly, prior research conducted in our group has shown that alveolar cell proliferation in response to airway injury does not occur in the aged mouse lung. Thus, the proposed studies can provide insight on how changes in the aged lung impact lung progenitor cell function. This is directly relevant to the parent grant, particularly for Aim 1, which involves characterizing the cellular states of alveolar progenitor cells. We expect her proposed studies will have important implications for chronic lung diseases like COPD as well as lung cancer, for which aging is a major risk factor. The results of this work will also help us continue to better models of lung cancer in the aged lung and to learn ways to intervene in lung cancer and lung diseases associated with age.