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Macrophage Responses to Epithelial Dysfunction Promote Lung Fibrosis in Aging

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Technical Report,30 Sep 2016,29 Sep 2017

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Northwestern University Chicago United States

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Purpose To test the hypothesis that the replacement of tissue-resident alveolar macrophages with monocyte-derived macrophages in response to repeated injury over the lifespan explains the delayed onset of lung fibrosis until the later decades of life. We will use our experimental findings in mice to guide an unbiased assessment of macrophage heterogeneity in normal human lungs and lungs from patients with pulmonary fibrosis. The overarching goal of these studies is to identify clinically applicable biomarkers that can guide therapy and factors released from tissue-resident macrophages or bone marrow-derived macrophages that prevent or promote fibrosis, respectively so they can be targeted for prevention or therapy. This hypothesis will be tested in the following aims Aim 1 To determine whether replacement of tissue-resident alveolar macrophages by monocyte-derived alveolar macrophages during aging contributes to the enhanced susceptibility to lung fibrosis in aged mice. Aim 2 To determine whether tissue-resident alveolar macrophages or monocyte-derived alveolar macrophages differentially respond to epithelial injury in a murine model of accelerated pulmonary fibrosis. Aim 3 To identify novel biomarkers expressed by human tissue-resident and monocyte-derived alveolar macrophages based on single cell molecular classification in patients with pulmonary fibrosis.

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  • Medicine and Medical Research

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