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

Authors :
Emily Fraser
Laura Denney
Agne Antanaviciute
Karl Blirando
Chaitanya Vuppusetty
Yuejuan Zheng
Emmanouela Repapi
Valentina Iotchkova
Stephen Taylor
Neil Ashley
Victoria St Noble
Rachel Benamore
Rachel Hoyles
Colin Clelland
Joseph M. D. Rastrick
Clare S. Hardman
Nasullah K. Alham
Rachel E. Rigby
Alison Simmons
Jan Rehwinkel
Ling-Pei Ho
Source :
Frontiers in Immunology, Vol 12 (2021)
Publication Year :
2021
Publisher :
Frontiers Media S.A., 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.

Details

Language :
English
ISSN :
16643224
Volume :
12
Database :
Directory of Open Access Journals
Journal :
Frontiers in Immunology
Publication Type :
Academic Journal
Accession number :
edsdoj.2bf92ce74a22443b86f715dc1150d4d6
Document Type :
article
Full Text :
https://doi.org/10.3389/fimmu.2021.623430