The transferrin receptor CD71 delineates functionally distinct airway macrophage subsets during idiopathic pulmonary fibrosis

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Title: The transferrin receptor CD71 delineates functionally distinct airway macrophage subsets during idiopathic pulmonary fibrosis
Authors: Allden, SJ
Ogger, PP
Ghai, P
McErlean, P
Hewitt, R
Toshner, R
Walker, SA
Saunders, P
Kingston, S
Molyneaux, PL
Maher, TM
Lloyd, CM
Byrne, AJ
Item Type: Journal Article
Abstract: RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a devastating progressive disease with limited therapeutic options. Airway macrophages (AMs) are key components of the defence of the airways and are implicated in the pathogenesis of IPF. Alterations in iron metabolism have been described during fibrotic lung disease and in murine models of lung fibrosis. However, the role of transferrin receptor-1 (CD71)-expressing AMs in IPF is not known. OBJECTIVES: To assess the role of CD71 expressing AMs in the IPF-lung. METHODS: We utilized multi-parameter flow cytometry, gene expression analysis and phagocytosis/transferrin uptake assays to delineate the role of AMs expressing, or lacking, CD71 in the BAL of patients with IPF or healthy controls. MEASUREMENTS AND MAIN RESULTS: There was a distinct increase in proportions of AMs lacking CD71 in IPF patients in comparison to healthy controls. Levels of BAL transferrin were enhanced in IPF-BAL and furthermore, CD71- AMs had an impaired ability to sequester transferrin. CD71+ and CD71- AMs were phenotypically, functionally and transcriptionally distinct, with CD71- AMs characterised by reduced expression of markers of macrophage maturity, impaired phagocytosis and enhanced expression of pro-fibrotic genes. Importantly, proportions of AMs lacking CD71 were independently associated with worse survival, underlining the importance of this population in IPF and as a potential therapeutic target. CONCLUSIONS: Taken together these data highlight how CD71 delineates AM subsets which play distinct roles in IPF and furthermore, CD71- AMs may be an important pathogenic component of fibrotic lung disease.
Issue Date: 15-Jul-2019
Date of Acceptance: 2-May-2019
URI: http://hdl.handle.net/10044/1/70043
DOI: https://doi.org/10.1164/rccm.201809-1775OC
ISSN: 1073-449X
Publisher: American Thoracic Society
Journal / Book Title: American Journal of Respiratory and Critical Care Medicine
Volume: 200
Issue: 2
Copyright Statement: © 2019 by the American Thoracic Society. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: Wellcome Trust
National Heart & Lung Institute Foundation
Asthma UK
The Royal Society
Wellcome Trust
National Institute for Health Research
UCB Celltech Ltd
British Lung Foundation
Funder's Grant Number: 205949/Z/17/Z
Students 2016-19
AUK-SCF-2017-381
RSG/R1/180264
107059/Z/15/Z
CS-2013-13-017
PO 4400123668
C17-3
Keywords: Science & Technology
Life Sciences & Biomedicine
Critical Care Medicine
Respiratory System
General & Internal Medicine
airway macrophages
idiopathic pulmonary fibrosis
transferrin receptor
FLOW-CYTOMETRIC ANALYSIS
ALVEOLAR MACROPHAGES
IRON HOMEOSTASIS
LUNG
CELLS
EXACERBATIONS
MICROBIOME
GENERATION
MONOCYTES
FERRITIN
airway macrophages
idiopathic pulmonary fibrosis
transferrin receptor
Airway Macrophages
Idiopathic Pulmonary Fibrosis
Transferrin Receptor
Respiratory System
11 Medical and Health Sciences
Publication Status: Published
Conference Place: United States
Online Publication Date: 2019-05-03
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



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