دورية أكاديمية
Single Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis.
| العنوان: | Single Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis. |
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| المؤلفون: | Zhao AY; Yale School of Medicine, Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, New Haven, Connecticut, United States., Unterman A; Tel Aviv Sourasky Medical Center, Pulmonary Institute, Tel Aviv, Israel., Abu Hussein NS; Yale School of Medicine, Kaminiski Lab, New Haven, Connecticut, United States., Sharma P; Yale School of Medicine, Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, New Haven, Connecticut, United States., Nekola F; Yale School of Medicine, Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, New Haven, Connecticut, United States., Flint J; Yale School of Medicine, PCCSM, New Haven, Connecticut, United States., Yan X; Yale School of Medicine, Section of Pulmonary, Critical Care and Sleep Medicine, New Haven, Connecticut, United States., Adams TS; Yale University School of Medicine, Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, New Haven, Connecticut, United States., Justet A; Yale University School of Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New Haven, Connecticut, United States.; Normandie University, Service de Pneumologie, CHU de Caen; UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, GIP CYCERON, Caen, France., Sumida TS; Yale University, Neurology, New Haven, Connecticut, United States., Zhao J; Yale University, Section of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New Haven, Connecticut, United States., Schupp JC; Yale University, Section of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New Haven, Connecticut, United States.; Hannover Medical School, Department of Pulmonary and Infectious Diseases, Hannover, Niedersachsen, Germany., Raredon MSB; Yale University, Section of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New Haven, Connecticut, United States.; Yale University, Department of Anesthesiology, New Haven, Connecticut, United States.; Yale University, Department of Immunobiology, New Haven, Connecticut, United States., Ahangari F; Yale University, Pulmonary Critical Care and Sleep Medicine, New Haven, Connecticut, United States., Deluliis G; Yale School of Medicine, Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, New Haven, Connecticut, United States., Zhang Y; University of Pittsburgh, Medicine, Pittsburgh, Pennsylvania, United States., Buendia-Roldan I; Instituto Nacional de Enfermedades Respiratorias, Traslational research in aging and lung fibrosis, Mexico, Mexico., Adegunsoye A; University of Chicago Pritzker School of Medicine, Section of Pulmonary/Critical Care, Department of Medicine, Chicago, Illinois, United States., Sperling AI; University of Virginia, Division of Pulmonary and Critical Care Medicine, Department of Medicine,, Charlottesville, Virginia, United States., Prasse A; Medizinische Hochschule Hannover, Pulmonology, Hannover, Germany.; Fraunhofer ITEM, Clinical Research Center, Hannover, Germany., Ryu C; Yale University School of Medicine, Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine , New Haven, Connecticut, United States., Herzog E; Yale School of Medicine, New Haven, Connecticut, United States., Selman M; Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico., Pardo A; Universidad Nacional Autónoma de México, Facultad de Ciencias, México DF, Mexico., Kaminski N; Yale School of Medicine , Pulmonary, Critical Care and Sleep Mediine , New Haven, Connecticut, United States; naftali.kaminski@yale.edu. |
| المصدر: | American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2024 Jun 26. Date of Electronic Publication: 2024 Jun 26. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Thoracic Society Country of Publication: United States NLM ID: 9421642 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1535-4970 (Electronic) Linking ISSN: 1073449X NLM ISO Abbreviation: Am J Respir Crit Care Med Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2000- : New York, NY : American Thoracic Society Original Publication: New York, NY : American Lung Association, c1994- |
| مستخلص: | Rationale : Fibrotic hypersensitivity pneumonitis is a debilitating interstitial lung disease driven by incompletely understood immune mechanisms. Objectives : To elucidate immune aberrations in fibrotic hypersensitivity pneumonitis in single-cell resolution. Methods : Single-cell 5' RNA sequencing was conducted on peripheral blood mononuclear cells and bronchoalveolar lavage cells obtained from 45 patients with fibrotic hypersensitivity pneumonitis, 63 idiopathic pulmonary fibrosis, 4 non-fibrotic hypersensitivity pneumonitis, and 36 healthy controls in the United States and Mexico. Analyses included differential gene expression (Seurat), transcription factor activity imputation (DoRothEA-VIPER), and trajectory analyses (Monocle3/Velocyto-scVelo-CellRank). Measurements and Main Results : Overall, 501,534 peripheral blood mononuclear cells from 110 patients and controls and 88,336 bronchoalveolar lavage cells from 19 patients were profiled. Compared to controls, fibrotic hypersensitivity pneumonitis has elevated classical monocytes (adjusted-p=2.5e-3) and are enriched in CCL3 hi /CCL4 hi and S100A hi classical monocytes (adjusted-p<2.2e-16). Trajectory analyses demonstrate that S100A hi classical monocytes differentiate into SPP1 hi lung macrophages associated with fibrosis. Compared to both controls and idiopathic pulmonary fibrosis, fibrotic hypersensitivity pneumonitis patient cells are significantly enriched in GZM hi cytotoxic T cells. These cells exhibit transcription factor activities indicative of TGFβ and TNFα/NFκB pathways. These results are publicly available at https://ildimmunecellatlas.org. Conclusions : Single-cell transcriptomics of fibrotic hypersensitivity pneumonitis patients uncovered novel immune perturbations, including previously undescribed increases in GZM hi cytotoxic CD4+ and CD8+ T cells - reflecting this disease's unique inflammatory T-cell driven nature - as well as increased S100A hi and CCL3 hi /CCL4 hi classical monocytes also observed in idiopathic pulmonary fibrosis. Both cell populations may guide the development of new biomarkers and therapeutic interventions. |
| فهرسة مساهمة: | Keywords: fibrotic hypersensitivity pneumonitis; idiopathic pulmonary fibrosis; interstitial lung disease; single-cell RNA sequencing; usual interstitial pneumonia |
| تواريخ الأحداث: | Date Created: 20240626 Latest Revision: 20240709 |
| رمز التحديث: | 20240710 |
| DOI: | 10.1164/rccm.202401-0078OC |
| PMID: | 38924775 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1535-4970 |
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| DOI: | 10.1164/rccm.202401-0078OC |