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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1437224
This article is part of the Research Topic The Biological / Pathological Role of IL-32 in Health / Disease View all 5 articles
IL-2 and TCR stimulation induce expression and secretion of IL-32β by human T cells
Provisionally accepted- 1 Interventional Immunology, Leibniz Institute for Immunotherapy, Regensburg, Bavaria, Germany
- 2 Algorithmic Bioinformatics, Leibniz Institute for Immunotherapy, Regensburg, Bavaria, Germany
- 3 Department of Internal Medicine III, Hematology and Medical Oncology, University Medical Center, Regensburg, Bavaria, Germany
- 4 Bavarian Cancer Research Center (BZKF), Regensburg, Germany
- 5 Department of Biosystems Science and Engineering, ETH Zurich, Zurich, Zürich, Switzerland
IL-32 expression is important for pathogen clearance but detrimental in chronic inflammation, autoimmunity, and cancer. T cells are major IL-32 producers in these diseases and key mediators of pathogen and tumor elimination but also autoimmune destruction. However, their contribution to IL-32 biology during immune responses is hardly understood due to several isoforms with divergent inflammatory properties. Here, we identified IL-32β as the predominant isoform in various T cell subsets of healthy individuals and breast cancer patients with the highest levels detected in intratumoral regulatory T cells. We show that IL-32β is induced by IL-2 but IL-32β release requires T Cell Receptor rather than IL2R stimulation. Using inhibitors of protein secretion pathways and serial (ultra)centrifugation of T cell supernatants, we demonstrate that T cells actively secrete IL-32β unconventionally, as a free protein and, to a minor degree, through exosomes. Thus, our data identify activated T cells as major IL-32β secretors in health and cancer.
Keywords: IL-32 isoform, IL-32β, IL-32 secretion mechanism, T cells, Exosomes, Unconventional secretion pathway, IL-2, Cancer
Received: 23 May 2024; Accepted: 22 Jul 2024.
Copyright: © 2024 Durst, Benešová, Pervan, Krenz, Wurzel, Lohmayer, Mühlbauer, Wöllner, Köhl, Menevse, Stamova, Volpin, Beckhove and Xydia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Maria Xydia, Interventional Immunology, Leibniz Institute for Immunotherapy, Regensburg, Bavaria, Germany
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