期刊
FRONTIERS IN IMMUNOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.623430
关键词
monocytes; lung; fibrosis; idiopathic pulmonary fibrosis; macrophages
类别
资金
- National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC)
- Medical Research Council UK [MC_UU_00008/1]
- Oxford-UCB Alliance research grant
- Oxford NIHR Biomedical Research Centre (Molecular Diagnostics Theme/Experimental Pathology sub-theme) Cancer Research UK (CR-UK) through the Cancer Research UK Oxford Centre [C5255/A18085]
- Pathological Society of Great Britain and Ireland
Monocytes in idiopathic pulmonary fibrosis (IPF) patients exhibit a distinct immunophenotype from age-matched controls, with an activated type I interferon pathway that may contribute to driving chronic inflammation and fibrosis. These findings strengthen the potential role of monocytes in the pathogenesis of IPF.
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 (Fc gamma R1) 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 CD64(hi) 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.
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