Targeting Immunological Pathways in Chronic Lung Allograft Dysfunction

Scope: Using causal experiments in mouse models of pulmonary fibrosis and unbiased profiling of the samples derived from patients with pulmonary fibrosis we have demonstrated that monocyte-derived alveolar macrophages drive pulmonary fibrosis. Our published and preliminary data support our hypothesis that monocyte-derived alveolar macrophages (MoAM) provide a necessary and specific link between the injured epithelium and dysregulated myofibroblast proliferation in CLAD and other fibrotic lung diseases. Targeting this pathogenic non-resident cell population may therefore favor epithelial repair over fibrosis, preserving allograft function. Our molecular profiling suggests that these pathogenic cells are maintained via autocrine M-CSF/M-CSF-R signaling, which are amenable to pharmacological targeting.