Multi-Modal Characterization of Monocytes in Idiopathic Pulmonary Fibrosis Reveals a Primed Type I Interferon Immune Phenotype

Front Immunol. 2021 Mar 5;12:623430. doi: 10.3389/fimmu.2021.623430. eCollection 2021.

Abstract

Idiopathic pulmonary fibrosis (IPF) is the most severe form of chronic lung fibrosis. Circulating monocytes have been implicated in immune pathology in IPF but their phenotype is unknown. In this work, we determined the immune phenotype of monocytes in IPF using multi-colour flow cytometry, RNA sequencing and corresponding serum factors, and mapped the main findings to amount of lung fibrosis and single cell transcriptomic landscape of myeloid cells in IPF lungs. We show that monocytes from IPF patients displayed increased expression of CD64 (FcγR1) which correlated with amount of lung fibrosis, and an amplified type I IFN response ex vivo. These were accompanied by markedly raised CSF-1 levels, IL-6, and CCL-2 in serum of IPF patients. Interrogation of single cell transcriptomic data from human IPF lungs revealed increased proportion of CD64hi monocytes and "transitional macrophages" with higher expression of CCL-2 and type I IFN genes. Our study shows that monocytes in IPF patients are phenotypically distinct from age-matched controls, with a primed type I IFN pathway that may contribute to driving chronic inflammation and fibrosis. These findings strengthen the potential role of monocytes in the pathogenesis of IPF.

Keywords: fibrosis; idiopathic pulmonary fibrosis; lung; macrophages; monocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Cells, Cultured
  • Chemokine CCL2 / blood
  • Flow Cytometry
  • Gene Expression Profiling
  • Humans
  • Idiopathic Pulmonary Fibrosis / genetics
  • Idiopathic Pulmonary Fibrosis / immunology*
  • Idiopathic Pulmonary Fibrosis / metabolism
  • Idiopathic Pulmonary Fibrosis / pathology
  • Immunophenotyping
  • Interferon Type I / genetics
  • Interferon Type I / metabolism*
  • Interleukin-6 / blood
  • Lung / immunology*
  • Lung / metabolism
  • Lung / pathology
  • Macrophage Colony-Stimulating Factor / blood
  • Macrophages / immunology
  • Macrophages / metabolism
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Phenotype
  • Receptors, IgG / genetics
  • Receptors, IgG / metabolism
  • Single-Cell Analysis

Substances

  • CCL2 protein, human
  • CSF1 protein, human
  • Chemokine CCL2
  • IL6 protein, human
  • Interferon Type I
  • Interleukin-6
  • Receptors, IgG
  • Macrophage Colony-Stimulating Factor