University of Oulu

Laura Kummola, Tanja Salomaa, Zsuzsanna Ortutay, Ram Savan, Howard A. Young, Ilkka S. Junttila, IL-4, IL-13 and IFN-γ -induced genes in highly purified human neutrophils, Cytokine, Volume 164, 2023, 156159, ISSN 1043-4666,

IL-4, IL-13 and IFN-γ -induced genes in highly purified human neutrophils

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Author: Kummola, Laura1; Salomaa, Tanja2,3; Ortutay, Zsuzsanna4;
Organizations: 1Biodiversity Interventions for Well-being, Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland
2Cytokine Biology Research Group, Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland
3Fimlab Laboratories, 33520 Tampere, Finland
4HiDucator Oy, 36200 Kangasala, Finland
5Department of Immunology, School of Medicine, University of Washington, 98195 Seattle, WA, USA
6Center for Cancer Research, National Cancer Institute, 21702 Frederick, MD, USA
7Northern Finland Laboratory Centre (NordLab), 90220 Oulu, Finland
8Research Unit of Biomedicine, University of Oulu, 90570 Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.8 MB)
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Language: English
Published: Elsevier, 2023
Publish Date: 2023-03-27


Interleukin (IL)-4 and IL-13 are related cytokines with well-known specific roles in type 2 immune response. However, their effects on neutrophils are not completely understood. For this, we studied human primary neutrophil responses to IL-4 and IL-13. Neutrophils are dose-dependently responsive to both IL-4 and IL-13 as indicated by signal transducer and activator of transcription 6 (STAT6) phosphorylation upon stimulation, with IL-4 being more potent inducer of STAT6. IL-4-, IL-13- and Interferon (IFN)-γ-stimulated gene expression in highly purified human neutrophils induced both overlapping and unique gene expression in highly purified human neutrophils. IL-4 and IL-13 specifically regulate several immune-related genes, including IL-10, tumor necrosis factor (TNF) and leukemia inhibitory factor (LIF), while type1 immune response-related IFN-γ induced gene expression related for example, to intracellular infections. In analysis of neutrophil metabolic responses, oxygen independent glycolysis was specifically regulated by IL-4, but not by IL-13 or IFN-γ, suggesting specific role for type I IL-4 receptor in this process. Our results provide a comprehensive analysis of IL-4, IL-13 and IFN-γ -induced gene expression in neutrophils while also addressing cytokine-mediated metabolic changes in neutrophils.

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Series: Cytokine
ISSN: 1043-4666
ISSN-E: 1096-0023
ISSN-L: 1043-4666
Volume: 164
Article number: 156159
DOI: 10.1016/j.cyto.2023.156159
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Funding: This work was financially supported by the Academy of Finland (IJ; Grants 25013080481 and 25013142041), the Competitive State Research Financing of the Expert Responsibility area of Fimlab Laboratories (IJ; Grant X51409), Tampere Tuberculosis Foundation (IJ), Sigrid Juselius Foundation (IJ), Finnish Medical Foundation (IJ), Tampere Children’s Hospital Support Association (IJ), and City of Tampere Science Foundation (LK), Nordlab Laboratories (IJ; Grant X3710-KT0011) and Orion research foundation (TS). This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute (NCI), Cancer Innovation Laboratory (CIL) under grant No. 1ZIABC009283-36. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government.
Copyright information: © 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (