IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-43573-9.html
   My bibliography  Save this article

Human and mouse neutrophils share core transcriptional programs in both homeostatic and inflamed contexts

Author

Listed:
  • Nicolaj S. Hackert

    (Heidelberg University Hospital
    Heidelberg University Hospital
    Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Felix A. Radtke

    (Heidelberg University Hospital
    Heidelberg University Hospital
    Brigham and Women’s Hospital, Harvard Medical School
    University of Oxford)

  • Tarik Exner

    (Heidelberg University Hospital
    Heidelberg University Hospital)

  • Hanns-Martin Lorenz

    (Heidelberg University Hospital)

  • Carsten Müller-Tidow

    (Heidelberg University Hospital
    University of Heidelberg)

  • Peter A. Nigrovic

    (Harvard Medical School
    Brigham and Women’s Hospital, Harvard Medical School)

  • Guido Wabnitz

    (Heidelberg University Hospital)

  • Ricardo Grieshaber-Bouyer

    (Heidelberg University Hospital
    Heidelberg University Hospital
    University of Heidelberg
    Friedrich Alexander Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen)

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.

Suggested Citation

  • Nicolaj S. Hackert & Felix A. Radtke & Tarik Exner & Hanns-Martin Lorenz & Carsten Müller-Tidow & Peter A. Nigrovic & Guido Wabnitz & Ricardo Grieshaber-Bouyer, 2023. "Human and mouse neutrophils share core transcriptional programs in both homeostatic and inflamed contexts," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43573-9
    DOI: 10.1038/s41467-023-43573-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-43573-9
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-43573-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Zhang Bin & Horvath Steve, 2005. "A General Framework for Weighted Gene Co-Expression Network Analysis," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 4(1), pages 1-45, August.
    2. J. Casulli & M. E. Fife & S. A. Houston & S. Rossi & J. Dow & E. D. Williamson & G. C Clark & T. Hussell & R. V. D’Elia & M. A Travis, 2019. "CD200R deletion promotes a neutrophil niche for Francisella tularensis and increases infectious burden and mortality," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    3. Bates, Douglas & Mächler, Martin & Bolker, Ben & Walker, Steve, 2015. "Fitting Linear Mixed-Effects Models Using lme4," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 67(i01).
    4. Shani Talia Gal-Oz & Barbara Maier & Hideyuki Yoshida & Kumba Seddu & Nitzan Elbaz & Charles Czysz & Or Zuk & Barbara E. Stranger & Hadas Ner-Gaon & Tal Shay, 2019. "ImmGen report: sexual dimorphism in the immune system transcriptome," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    5. Ricardo Grieshaber-Bouyer & Felix A. Radtke & Pierre Cunin & Giuseppina Stifano & Anaïs Levescot & Brinda Vijaykumar & Nathan Nelson-Maney & Rachel B. Blaustein & Paul A. Monach & Peter A. Nigrovic, 2021. "The neutrotime transcriptional signature defines a single continuum of neutrophils across biological compartments," Nature Communications, Nature, vol. 12(1), pages 1-21, December.
    6. Alexis J. Combes & Tristan Courau & Nicholas F. Kuhn & Kenneth H. Hu & Arja Ray & William S. Chen & Nayvin W. Chew & Simon J. Cleary & Divyashree Kushnoor & Gabriella C. Reeder & Alan Shen & Jessica T, 2021. "Global absence and targeting of protective immune states in severe COVID-19," Nature, Nature, vol. 591(7848), pages 124-130, March.
    7. Seth B. Coffelt & Kelly Kersten & Chris W. Doornebal & Jorieke Weiden & Kim Vrijland & Cheei-Sing Hau & Niels J. M. Verstegen & Metamia Ciampricotti & Lukas J. A. C. Hawinkels & Jos Jonkers & Karin E., 2015. "IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis," Nature, Nature, vol. 522(7556), pages 345-348, June.
    8. Alexis J. Combes & Tristan Courau & Nicholas F. Kuhn & Kenneth H. Hu & Arja Ray & William S. Chen & Nayvin W. Chew & Simon J. Cleary & Divyashree Kushnoor & Gabriella C. Reeder & Alan Shen & Jessica T, 2021. "Publisher Correction: Global absence and targeting of protective immune states in severe COVID-19," Nature, Nature, vol. 596(7872), pages 8-8, August.
    9. Bukyung Baik & Sora Yoon & Dougu Nam, 2020. "Benchmarking RNA-seq differential expression analysis methods using spike-in and simulation data," PLOS ONE, Public Library of Science, vol. 15(4), pages 1-19, April.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Quy Xiao Xuan Lin & Deepa Rajagopalan & Akshamal M. Gamage & Le Min Tan & Prasanna Nori Venkatesh & Wharton O. Y. Chan & Dilip Kumar & Ragini Agrawal & Yao Chen & Siew-Wai Fong & Amit Singh & Louisa J, 2024. "Longitudinal single cell atlas identifies complex temporal relationship between type I interferon response and COVID-19 severity," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Elvira Mennillo & Yang Joon Kim & Gyehyun Lee & Iulia Rusu & Ravi K. Patel & Leah C. Dorman & Emily Flynn & Stephanie Li & Jared L. Bain & Christopher Andersen & Arjun Rao & Stanley Tamaki & Jessica T, 2024. "Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    3. Jillian R. Jaycox & Carolina Lucas & Inci Yildirim & Yile Dai & Eric Y. Wang & Valter Monteiro & Sandra Lord & Jeffrey Carlin & Mariko Kita & Jane H. Buckner & Shuangge Ma & Melissa Campbell & Albert , 2023. "SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    4. Kami Pekayvaz & Alexander Leunig & Rainer Kaiser & Markus Joppich & Sophia Brambs & Aleksandar Janjic & Oliver Popp & Daniel Nixdorf & Valeria Fumagalli & Nora Schmidt & Vivien Polewka & Afra Anjum & , 2022. "Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    5. Alice Mac Kain & Ghizlane Maarifi & Sophie-Marie Aicher & Nathalie Arhel & Artem Baidaliuk & Sandie Munier & Flora Donati & Thomas Vallet & Quang Dinh Tran & Alexandra Hardy & Maxime Chazal & François, 2022. "Identification of DAXX as a restriction factor of SARS-CoV-2 through a CRISPR/Cas9 screen," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    6. Yvonne M. Mueller & Thijs J. Schrama & Rik Ruijten & Marco W. J. Schreurs & Dwin G. B. Grashof & Harmen J. G. van de Werken & Giovanna Jona Lasinio & Daniel Álvarez-Sierra & Caoimhe H. Kiernan & Melis, 2022. "Stratification of hospitalized COVID-19 patients into clinical severity progression groups by immuno-phenotyping and machine learning," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    7. Lucile P. A. Neyton & Ravi K. Patel & Aartik Sarma & Andrew Willmore & Sidney C. Haller & Kirsten N. Kangelaris & Walter L. Eckalbar & David J. Erle & Matthew F. Krummel & Carolyn M. Hendrickson & Pre, 2024. "Distinct pulmonary and systemic effects of dexamethasone in severe COVID-19," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    8. JANSSENS, Jochen & DE CORTE, Annelies & SÖRENSEN, Kenneth, 2016. "Water distribution network design optimisation with respect to reliability," Working Papers 2016007, University of Antwerp, Faculty of Business and Economics.
    9. Raymond Hernandez & Elizabeth A. Pyatak & Cheryl L. P. Vigen & Haomiao Jin & Stefan Schneider & Donna Spruijt-Metz & Shawn C. Roll, 2021. "Understanding Worker Well-Being Relative to High-Workload and Recovery Activities across a Whole Day: Pilot Testing an Ecological Momentary Assessment Technique," IJERPH, MDPI, vol. 18(19), pages 1-17, October.
    10. Christopher Hassall & Michael Nisbet & Evan Norcliffe & He Wang, 2024. "The Potential Health Benefits of Urban Tree Planting Suggested through Immersive Environments," Land, MDPI, vol. 13(3), pages 1-12, February.
    11. Jie Zhao & Ji Chen & Damien Beillouin & Hans Lambers & Yadong Yang & Pete Smith & Zhaohai Zeng & Jørgen E. Olesen & Huadong Zang, 2022. "Global systematic review with meta-analysis reveals yield advantage of legume-based rotations and its drivers," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    12. Elisabeth Beckmann & Lukas Olbrich & Joseph Sakshaug, 2024. "Multivariate assessment of interviewer-related errors in a cross-national economic survey (Lukas Olbrich, Elisabeth Beckmann, Joseph W. Sakshaug)," Working Papers 253, Oesterreichische Nationalbank (Austrian Central Bank).
    13. F J Heather & D Z Childs & A M Darnaude & J L Blanchard, 2018. "Using an integral projection model to assess the effect of temperature on the growth of gilthead seabream Sparus aurata," PLOS ONE, Public Library of Science, vol. 13(5), pages 1-19, May.
    14. Valentina Krenz & Arjen Alink & Tobias Sommer & Benno Roozendaal & Lars Schwabe, 2023. "Time-dependent memory transformation in hippocampus and neocortex is semantic in nature," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    15. Morán-Ordóñez, Alejandra & Ameztegui, Aitor & De Cáceres, Miquel & de-Miguel, Sergio & Lefèvre, François & Brotons, Lluís & Coll, Lluís, 2020. "Future trade-offs and synergies among ecosystem services in Mediterranean forests under global change scenarios," Ecosystem Services, Elsevier, vol. 45(C).
    16. Yixuan Qiu & Jing Lei & Kathryn Roeder, 2023. "Gradient-based sparse principal component analysis with extensions to online learning," Biometrika, Biometrika Trust, vol. 110(2), pages 339-360.
    17. Jack McDonnell & Thomas McKenna & Kathryn A. Yurkonis & Deirdre Hennessy & Rafael Andrade Moral & Caroline Brophy, 2023. "A Mixed Model for Assessing the Effect of Numerous Plant Species Interactions on Grassland Biodiversity and Ecosystem Function Relationships," Journal of Agricultural, Biological and Environmental Statistics, Springer;The International Biometric Society;American Statistical Association, vol. 28(1), pages 1-19, March.
    18. Ana Pinto & Tong Yin & Marion Reichenbach & Raghavendra Bhatta & Pradeep Kumar Malik & Eva Schlecht & Sven König, 2020. "Enteric Methane Emissions of Dairy Cattle Considering Breed Composition, Pasture Management, Housing Conditions and Feeding Characteristics along a Rural-Urban Gradient in a Rising Megacity," Agriculture, MDPI, vol. 10(12), pages 1-18, December.
    19. Damian M. Herz & Manuel Bange & Gabriel Gonzalez-Escamilla & Miriam Auer & Keyoumars Ashkan & Petra Fischer & Huiling Tan & Rafal Bogacz & Muthuraman Muthuraman & Sergiu Groppa & Peter Brown, 2022. "Dynamic control of decision and movement speed in the human basal ganglia," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    20. Ruiz Vargas, E. & Mitchell, D.G.V. & Greening, S.G. & Wahl, L.M., 2014. "Topology of whole-brain functional MRI networks: Improving the truncated scale-free model," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 405(C), pages 151-158.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43573-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.