Altered expression of CSF1R in airway macrophages during idiopathic pulmonary fibrosis

IPF is a progressive disease characterized by deposition of excessive ECM in the lung parenchyma. There is significant unmet need to understand IPF pathogenesis and to develop new therapies. Colony-stimulating factor (CSF)-1 is a key regulator of the mononuclear phagocyte system. CSF1 mediates its effects via binding the tyrosine kinase, CSF1 receptor (CSF1R). The CSF1–CSF1R pathway has emerged as a therapeutic target in IPF. Recently, we reported that levels of soluble CSF1R, were increased in the bronchoalveolar lavage (BAL) of patients with IPF and predicted survival. However, how the expression of CSF1R is altered during IPF, and how CSF1R influences airway macrophage (AM) function during the disease, is not known. To investigate the distribution of CSF1R in the airways during IPF, we first analysed peripheral blood and bronchoalveolar lavage (BAL) fluid from IPF patients (n=15) by flow cytometry. Our data show that in the circulation, classical monocytes were the highest CSF1R expressing cell type. In BAL, >90% of cells expressing CSF1R were AMs. We next sorted AMs from BAL of healthy controls (n=7) or IPF patients (n=22) and assessed CSF1R expression by quantitative qPCR. Our data indicate that there is a significant increase in CSF1R expression in AMs from IPF patients compared to controls. Immunohistochemical analysis of lung sections from control tissue (n=10) showed limited CSF1R staining; whereas IPF sections (n=20) had high expression of CSF1R in tissue macrophages. Taken together, our data indicate that CSF1R is highly expressed in peripheral monocytes and lung macrophage populations during IPF and implicates the CSF1R pathway in disease pathogenesis.