Human and mouse neutrophils share core transcriptional programs in both homeostatic and inflamed contexts
Abstract Neutrophils are frequently studied in mouse models, but the extent to which findings translate to humans remains poorly defined. In an integrative analysis of 11 mouse and 13 human datasets, we find a strong correlation of neutrophil gene expression across species. In inflammation, neutroph...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-43573-9 |
| _version_ | 1827590413542752256 |
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| author | Nicolaj S. Hackert Felix A. Radtke Tarik Exner Hanns-Martin Lorenz Carsten Müller-Tidow Peter A. Nigrovic Guido Wabnitz Ricardo Grieshaber-Bouyer |
| author_facet | Nicolaj S. Hackert Felix A. Radtke Tarik Exner Hanns-Martin Lorenz Carsten Müller-Tidow Peter A. Nigrovic Guido Wabnitz Ricardo Grieshaber-Bouyer |
| author_sort | Nicolaj S. Hackert |
| collection | DOAJ |
| description | Abstract Neutrophils are frequently studied in mouse models, but the extent to which findings translate to humans remains poorly defined. In an integrative analysis of 11 mouse and 13 human datasets, we find a strong correlation of neutrophil gene expression across species. In inflammation, neutrophils display substantial transcriptional diversity but share a core inflammation program. This program includes genes encoding IL-1 family members, CD14, IL-4R, CD69, and PD-L1. Chromatin accessibility of core inflammation genes increases in blood compared to bone marrow and further in tissue. Transcription factor enrichment analysis implicates members of the NF-κB family and AP-1 complex as important drivers, and HoxB8 neutrophils with JunB knockout show a reduced expression of core inflammation genes in resting and activated cells. In independent single-cell validation data, neutrophil activation by type I or type II interferon, G-CSF, and E. coli leads to upregulation in core inflammation genes. In COVID-19 patients, higher expression of core inflammation genes in neutrophils is associated with more severe disease. In vitro treatment with GM-CSF, LPS, and type II interferon induces surface protein upregulation of core inflammation members. Together, we demonstrate transcriptional conservation in neutrophils in homeostasis and identify a core inflammation program shared across heterogeneous inflammatory conditions. |
| first_indexed | 2024-03-09T01:16:31Z |
| format | Article |
| id | doaj.art-58065059b946472fbbc1099bf5871d69 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-09T01:16:31Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-58065059b946472fbbc1099bf5871d692023-12-10T12:25:21ZengNature PortfolioNature Communications2041-17232023-12-0114112110.1038/s41467-023-43573-9Human and mouse neutrophils share core transcriptional programs in both homeostatic and inflamed contextsNicolaj S. Hackert0Felix A. Radtke1Tarik Exner2Hanns-Martin Lorenz3Carsten Müller-Tidow4Peter A. Nigrovic5Guido Wabnitz6Ricardo Grieshaber-Bouyer7Division of Rheumatology, Department of Medicine V, Heidelberg University HospitalDivision of Rheumatology, Department of Medicine V, Heidelberg University HospitalDivision of Rheumatology, Department of Medicine V, Heidelberg University HospitalDivision of Rheumatology, Department of Medicine V, Heidelberg University HospitalDepartment of Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University HospitalDivision of Immunology, Boston Children’s Hospital, Harvard Medical SchoolInstitute for Immunology, Heidelberg University HospitalDivision of Rheumatology, Department of Medicine V, Heidelberg University HospitalAbstract Neutrophils are frequently studied in mouse models, but the extent to which findings translate to humans remains poorly defined. In an integrative analysis of 11 mouse and 13 human datasets, we find a strong correlation of neutrophil gene expression across species. In inflammation, neutrophils display substantial transcriptional diversity but share a core inflammation program. This program includes genes encoding IL-1 family members, CD14, IL-4R, CD69, and PD-L1. Chromatin accessibility of core inflammation genes increases in blood compared to bone marrow and further in tissue. Transcription factor enrichment analysis implicates members of the NF-κB family and AP-1 complex as important drivers, and HoxB8 neutrophils with JunB knockout show a reduced expression of core inflammation genes in resting and activated cells. In independent single-cell validation data, neutrophil activation by type I or type II interferon, G-CSF, and E. coli leads to upregulation in core inflammation genes. In COVID-19 patients, higher expression of core inflammation genes in neutrophils is associated with more severe disease. In vitro treatment with GM-CSF, LPS, and type II interferon induces surface protein upregulation of core inflammation members. Together, we demonstrate transcriptional conservation in neutrophils in homeostasis and identify a core inflammation program shared across heterogeneous inflammatory conditions.https://doi.org/10.1038/s41467-023-43573-9 |
| spellingShingle | Nicolaj S. Hackert Felix A. Radtke Tarik Exner Hanns-Martin Lorenz Carsten Müller-Tidow Peter A. Nigrovic Guido Wabnitz Ricardo Grieshaber-Bouyer Human and mouse neutrophils share core transcriptional programs in both homeostatic and inflamed contexts Nature Communications |
| title | Human and mouse neutrophils share core transcriptional programs in both homeostatic and inflamed contexts |
| title_full | Human and mouse neutrophils share core transcriptional programs in both homeostatic and inflamed contexts |
| title_fullStr | Human and mouse neutrophils share core transcriptional programs in both homeostatic and inflamed contexts |
| title_full_unstemmed | Human and mouse neutrophils share core transcriptional programs in both homeostatic and inflamed contexts |
| title_short | Human and mouse neutrophils share core transcriptional programs in both homeostatic and inflamed contexts |
| title_sort | human and mouse neutrophils share core transcriptional programs in both homeostatic and inflamed contexts |
| url | https://doi.org/10.1038/s41467-023-43573-9 |
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