DNA methylome alterations are associated with airway macrophage differentiation and phenotype during lung fibrosis
| Autor: | Christopher G. Bell, Richard J. Hewitt, Philip L. Molyneaux, Gesa J. Albers, Shaun Kingston, Zabreen Busharat, Adam J. Byrne, Patricia P. Ogger, Clare M. Lloyd, Emily Calamita, Poonam Ghai, Peter McErlean, Toby M. Maher, Stephan Beck |
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| Přispěvatelé: | Action for Pulmonary Fibrosis |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Pulmonary and Respiratory Medicine
interstitial lung disease Lung DNA methylation epigenetics business.industry pathogenesis Respiratory disease Respiratory System Interstitial lung disease respiratory system Critical Care and Intensive Care Medicine medicine.disease Phenotype respiratory tract diseases Pathogenesis Idiopathic pulmonary fibrosis medicine.anatomical_structure Immunology Medicine Epigenetics business monocytes 11 Medical and Health Sciences |
| Popis: | Rationale: Airway macrophages (AMs) are key regulators of the lung environment and are implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF), a fatal respiratory disease with no cure. However, knowledge about the epigenetics of AMs in IPF is limited. Objectives: To assess the role of epigenetic regulation of AMs during lung fibrosis. Methods: We undertook DNA methylation (DNAm) profiling by using Illumina EPIC (850k) arrays in sorted AMs from healthy donors (n = 14) and donors with IPF (n = 30). Cell-type deconvolution was performed by using reference myeloid-cell DNA methylomes. Measurements and Main Results: Our analysis revealed that epigenetic heterogeneity was a key characteristic of IPF AMs. DNAm "clock" analysis indicated that epigenetic alterations in IPF AMs were not associated with accelerated aging. In differential DNAm analysis, we identified numerous differentially methylated positions (n = 11) and differentially methylated regions (n = 49) between healthy and IPF AMs, respectively. Differentially methylated positions and differentially methylated regions encompassed genes involved in lipid (LPCAT1 [lysophosphatidylcholine acyltransferase 1]) and glucose (PFKFB3 [6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3]) metabolism, and importantly, the DNAm status was associated with disease severity in IPF. Conclusions: Collectively, our data identify that changes in the epigenome are associated with the development and function of AMs in the IPF lung. |
| Databáze: | OpenAIRE |
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