Multiparameter Flow Cytometric Analysis of Human Alveolar Macrophages in Patients with Idiopathic Pulmonary Fibrosis: A Guide To Molecular Taxonomy of the Rare Disease and Personalized Treatment

Project: Research project

Project Details

Description

Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive and usually fatal disorder for which there are no treatments, except lung transplantation. Current classification of IPF is based on clinical features and does not reflect disease pathogenesis. Moreover, molecular markers to predict prognosis and guide therapy are limited. We and others have shown that lung macrophages play key roles in the development of lung fibrosis in murine models and data from patients with IPF and systemic sclerosis-associated lung fibrosis support this hypothesis. Our preliminary data suggest that, in contrast to a healthy lung, the population of alveolar macrophages during the pulmonary fibrosis is heterogeneous. We suggest that proteins expressed by subpopulations of alveolar macrophages may serve as biomarkers to predict clinical outcomes or guide therapy for patients with lung fibrosis. In addition, some of these proteins, or their downstream targets, might serve as novel therapeutic targets. Recently, several independent groups have used murine models to show that “tissue-resident” alveolar macrophages are a long-lived, self-renewing cell population with developmental origins outside the bone marrow. During lung injury and fibrosis peripheral blood monocytes enter the lung where they take on a phenotype similar to tissue-resident alveolar macrophages. Our group has used murine models and state of the art fate mapping techniques to definitively show that these “monocyte-derived” alveolar macrophages express markedly different levels of pro-inflammatory and pro-fibrotic genes during fibrosis. Furthermore, we have shown that these monocyte-derived alveolar macrophages persist in the lung for at least months after the resolution of injury or fibrosis. This lends support to the hypothesis that a sub-population of monocyte-derived alveolar macrophages, which expands in response to the injuries and insults associated with normal aging, drives the development of pulmon
StatusFinished
Effective start/end date3/26/153/26/16

Funding

  • Becton, Dickinson and Company (Agmt 3/26/15)

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