@article{a5d0beb4fdd04dcda85bf23c415e1420,
title = "IL-4, IL-13 and IFN-γ -induced genes in highly purified human neutrophils",
abstract = "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.",
keywords = "Allergy, IL-13, IL-4, Neutrophil, Signal transduction, Transcriptome, Type 2 immune response",
author = "Laura Kummola and Tanja Salomaa and Zsuzsanna Ortutay and Ram Savan and Young, {Howard A.} and Junttila, {Ilkka S.}",
note = "Funding Information: 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{\textquoteright}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. Funding Information: The authors acknowledge the Tampere facility of Flow Cytometry for their service. We also thank the Medical Bioinformatics Centre of Turku Bioscience Centre for the sequencing data analysis. The Centre is supported by University of Turku, {\AA}bo Akademi University, Biocenter Finland and Elixir-Finland. Timothy Myers at NIAID Genomic Technologies Section is thanked for invaluable help with initial genome-wide data analysis of neutrophils. Reija Autio at Tampere University is thanked for her assistance with statistical analyses. Dedicated to the memory of William E. Paul (1936-2015), who inspired and oversaw the first experiments of this work. Funding Information: The authors acknowledge the Tampere facility of Flow Cytometry for their service. We also thank the Medical Bioinformatics Centre of Turku Bioscience Centre for the sequencing data analysis. The Centre is supported by University of Turku, {\AA}bo Akademi University, Biocenter Finland and Elixir-Finland. Timothy Myers at NIAID Genomic Technologies Section is thanked for invaluable help with initial genome-wide data analysis of neutrophils. Reija Autio at Tampere University is thanked for her assistance with statistical analyses. Dedicated to the memory of William E. Paul (1936-2015), who inspired and oversaw the first experiments of this work. Publisher Copyright: {\textcopyright} 2023 The Author(s)",
year = "2023",
month = apr,
doi = "10.1016/j.cyto.2023.156159",
language = "English",
volume = "164",
journal = "CYTOKINE",
issn = "1043-4666",
publisher = "Elsevier",
}