AUTHOR=Sanna Franziska Christine , Benešová Iva , Pervan Philip , Krenz Adriana , Wurzel Alexander , Lohmayer Robert , Mühlbauer Jasmin , Wöllner Amélie , Köhl Nina , Menevse Ayse Nur , Stamova Slava , Volpin Valentina , Beckhove Philipp , Xydia Maria TITLE=IL-2 and TCR stimulation induce expression and secretion of IL-32β by human T cells JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1437224 DOI=10.3389/fimmu.2024.1437224 ISSN=1664-3224 ABSTRACT=

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.