Skip to main content

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
Franziska C. Durst Franziska C. Durst 1Iva Benešová Iva Benešová 1Philip Pervan Philip Pervan 1Adriana Krenz Adriana Krenz 1Alexander Wurzel Alexander Wurzel 1Robert Lohmayer Robert Lohmayer 1,2Jasmin Mühlbauer Jasmin Mühlbauer 1Amélie Wöllner Amélie Wöllner 3,4Nina Köhl Nina Köhl 3,4Ayse N. Menevse Ayse N. Menevse 1,5Slava Stamova Slava Stamova 1Valentina Volpin Valentina Volpin 1Philipp Beckhove Philipp Beckhove 1,3Maria Xydia Maria Xydia 1,4*
  • 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

The final, formatted version of the article will be published soon.

    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

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.