Type I interferon–activated myeloid states are associated with less fibrotic stages in idiopathic pulmonary fibrosis

Here, we integrate single cell transcriptomics of lung digest and bronchoalveolar-lavaged cells (n=108 patients), subcellular-resolution tissue spatial transcriptomics, and single-cell phospho-CyTOF of blood cells to define myeloid states associated with early stages of fibrosis. Two distinct myeloid gene transcriptional programmes are increased in IPF compared to non-diseased controls - type I interferon-activated and fibrotic remodelling programme.

At cell, organ and patient levels, cell types with increased type I interferon-activated programme (FABP4hi alveolar macrophages, classical monocytes, interstitial macrophages and non-classical monocytes) are associated with architecturally better-preserved lung tissue, the alveolar barrier and less fibrotic lung, or less severe disease. Circulating monocytes exhibited heightened type I interferon responsiveness that inversely correlated with severity of clinical disease.