AUTHOR=Fraser Emily , Denney Laura , Antanaviciute Agne , Blirando Karl , Vuppusetty Chaitanya , Zheng Yuejuan , Repapi Emmanouela , Iotchkova Valentina , Taylor Stephen , Ashley Neil , St Noble Victoria , Benamore Rachel , Hoyles Rachel , Clelland Colin , Rastrick Joseph M. D. , Hardman Clare S. , Alham Nasullah K. , Rigby Rachel E. , Simmons Alison , Rehwinkel Jan , Ho Ling-Pei TITLE=Multi-Modal Characterization of Monocytes in Idiopathic Pulmonary Fibrosis Reveals a Primed Type I Interferon Immune Phenotype JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.623430 DOI=10.3389/fimmu.2021.623430 ISSN=1664-3224 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.