Frontiers in Immunology (Aug 2024)

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

  • Franziska Christine Sanna,
  • Iva Benešová,
  • Philip Pervan,
  • Adriana Krenz,
  • Alexander Wurzel,
  • Robert Lohmayer,
  • Robert Lohmayer,
  • Jasmin Mühlbauer,
  • Amélie Wöllner,
  • Amélie Wöllner,
  • Nina Köhl,
  • Nina Köhl,
  • Ayse Nur Menevse,
  • Ayse Nur Menevse,
  • Slava Stamova,
  • Valentina Volpin,
  • Philipp Beckhove,
  • Philipp Beckhove,
  • Maria Xydia,
  • Maria Xydia

DOI
https://doi.org/10.3389/fimmu.2024.1437224
Journal volume & issue
Vol. 15

Abstract

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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.

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