Single-cell profiling reveals immune aberrations in progressive idiopathic pulmonary fibrosis
Single-cell profiling reveals immune aberrations in progressive idiopathic pulmonary fibrosis
Abstract RationaleChanges in peripheral blood cell populations have been observed but not detailed at single-cell resolution in idiopathic pulmonary fibrosis (IPF). ObjectivesTo provide an atlas of the changes in the peripheral immune system in stable and progressive IPF. MethodsPeripheral blood mononuclear cells (PBMCs) from IPF patients and controls were profiled using 10x Chromium 5’ single-cell RNA sequencing (scRNA-seq). Flow cytometry was used for validation. Protein concentrations of Regulatory T-cells (Tregs) and Monocytes chemoattractants were measured in plasma and lung homogenates from patients and controls. Measurements and Main ResultsThirty-eight PBMC samples from 25 patients with IPF and 13 matched controls yielded 149,564 cells that segregated into 23 subpopulations, corresponding to all expected peripheral blood cell populations. Classical monocytes were increased in progressive and stable IPF compared to controls (32.1%, 25.2%, 17.9%, respectively, p<0.05). Total lymphocytes were decreased in IPF vs controls, and in progressive vs stable IPF (52.6% vs 62.6%, p=0.035). Tregs were increased in progressive IPF (1.8% vs 1.1%, p=0.007), and were associated with decreased survival (P=0.009 in Kaplan-Meier analysis). Flow cytometry analysis confirmed this finding in an independent cohort of IPF patients. Tregs were also increased in two cohorts of lung scRNA-seq. CCL22 and CCL18, ligands for CCR4 and CCR8 Treg chemotaxis receptors, were increased in IPF. ConclusionsThe single-cell atlas of the peripheral immune system in IPF, reveals an outcome-predictive increase in classical monocytes and Tregs, as well as evidence for a lung-blood immune recruitment axis involving CCL7 (for classical monocytes) and CCL18/CCL22 (for Tregs).
Unterman Avraham、Schupp Jonas C.、Ishikawa Genta、Sumida Tomokazu S.、Gomez Jose L.、Herazo-Maya Jose、Cruz Charles S. Dela、Ryu Changwan、Sharma Prapti、Ahangari Farida、Flint Jasper、Zhao Amy Y.、Stein Yan、Kaminski Naftali、Herzog Erica L.、Neumark Nir、Cosme Carlos Jr.
Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University||Pulmonary Fibrosis Center of Excellence, Institute of Pulmonary Medicine, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University||Genomic Research Laboratory for Lung Fibrosis, Tel Aviv Sourasky Medical CenterSection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University||Department of Respiratory Medicine, Hannover Medical School (MHH)||Biomedical Research in End-Stage and Obstructive Lung Disease (BREATH), Hannover Medical School (MHH), German Center for Lung Research (DZL)Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale UniversityDepartment of Neurology, School of Medicine, Yale UniversitySection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale UniversityDivision of Pulmonary, Critical Care and Sleep Medicine, University of South Florida, Morsani College of MedicineSection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale UniversitySection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale UniversitySection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale UniversitySection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale UniversitySection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale UniversitySection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale UniversityPulmonary Fibrosis Center of Excellence, Institute of Pulmonary Medicine, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University||Genomic Research Laboratory for Lung Fibrosis, Tel Aviv Sourasky Medical CenterSection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale UniversitySection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale UniversitySection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale UniversitySection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, School of Medicine, Yale University
医药卫生理论医学研究方法基础医学
Idiopathic Pulmonary FibrosisSingle-cell RNA SequencingImmune SystemMonocytesRegulatory T Cells
Unterman Avraham,Schupp Jonas C.,Ishikawa Genta,Sumida Tomokazu S.,Gomez Jose L.,Herazo-Maya Jose,Cruz Charles S. Dela,Ryu Changwan,Sharma Prapti,Ahangari Farida,Flint Jasper,Zhao Amy Y.,Stein Yan,Kaminski Naftali,Herzog Erica L.,Neumark Nir,Cosme Carlos Jr..Single-cell profiling reveals immune aberrations in progressive idiopathic pulmonary fibrosis[EB/OL].(2025-03-28)[2025-07-18].https://www.medrxiv.org/content/10.1101/2023.04.29.23289296.点此复制
评论