IL-2 and TCR stimulation induce expression and secretion of IL-32β by human T cells

Autor: Franziska Christine Sanna, Iva Benešová, Philip Pervan, Adriana Krenz, Alexander Wurzel, Robert Lohmayer, Jasmin Mühlbauer, Amélie Wöllner, Nina Köhl, Ayse Nur Menevse, Slava Stamova, Valentina Volpin, Philipp Beckhove, Maria Xydia
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Frontiers in Immunology, Vol 15 (2024)
Druh dokumentu: article
ISSN: 1664-3224
DOI: 10.3389/fimmu.2024.1437224
Popis: 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.
Databáze: Directory of Open Access Journals