IL-32 表达对于病原体清除很重要，但对慢性炎症、自身免疫和癌症有害。 T 细胞是这些疾病中 IL-32 的主要产生者，也是病原体和肿瘤消除以及自身免疫破坏的关键介质。然而，由于几种具有不同炎症特性的亚型，人们很难理解它们在免疫反应过程中对 IL-32 生物学的贡献。在这里，我们确定 IL-32β 是健康个体和乳腺癌患者的各种 T 细胞亚型中的主要亚型，在瘤内调节性 T 细胞中检测到最高水平。我们发现 IL-32β 是由 IL-2 诱导的，但 IL-32β 的释放需要 T 细胞受体而不是 IL2R 刺激。使用蛋白质分泌途径的抑制剂和 T 细胞上清液的连续（超）离心，我们证明 T 细胞非常规地主动分泌 IL-32β，作为游离蛋白质，并在较小程度上通过外泌体分泌。因此，我们的数据确定激活的 T 细胞是健康和癌症中主要的 IL-32β 分泌者。版权所有 © 2024 Sanna、Benešová、Pervan、Krenz、Wurzel、Lohmayer、Mühlbauer、Wöllner、Köhl、Menevse、Stamova、Volpin、Beckhove 和 Xydia。

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.Copyright © 2024 Sanna, Benešová, Pervan, Krenz, Wurzel, Lohmayer, Mühlbauer, Wöllner, Köhl, Menevse, Stamova, Volpin, Beckhove and Xydia.