Active transcription in the vascular bed characterizes rapid progression in idiopathic pulmonary fibrosis

Idiopathic Pulmonary Fibrosis (IPF) is the most common manifestation of interstitial lung disease (ILD), with a median survival of 3-5 years after diagnosis. IPF is characterized by progressive fibrosis with the development of fibroblastic foci in the interstitium. Despite the short median survival, there is a striking variance in the clinical course of IPF, but the underlying biological mechanisms remain poorly understood. Here we used spatial transcriptomic analysis of IPF patients characterized as stable or rapid progressors (based on their decline in lung function and loss of forced vital capacity (FVC)), terminal-stage IPF subjects delineated for transplant, and 3 non IPF normal lung tissues (Clear margins from excision for pulmonary hamartoma). We investigated the presence of key transcriptional signatures using spatial transcriptomics (2). Briefly, sequential cuts of lung biopsies were stained with Trichrome, H&E, and immunofluorescently labeled to identify nuclei, fibroblasts (alpha smooth muscle actin, aSMA), and the vascular bed (CD31). Using a combination H&E and immunofluorescent staining, regions of interests (ROIs) were selected for transcriptional analysis. This study suggests a key role of the vascular bed in the progression of IPF, warranting further investigations. These data highlight distinct pathways of crosstalk between the fibroblasts and the vascular bed, which could prove central to the pathophysiology of the disease.