Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
Front Immunol. 2021 May 12;12:633586. doi: 10.3389/fimmu.2021.633586. eCollection 2021.
Myeloid cell interactions with cells of the adaptive immune system are an essential aspect of immunity. A key aspect of that interrelationship is its modulation by the microenvironment. Oxygen is known to influence myelosuppression of T cell activation in part the Hypoxia inducible (HIF) transcription factors. A number of drugs that act on the HIF pathway are currently in clinical use and it is important to evaluate how they act on immune cell function as part of a better understanding of how they will influence patient outcomes. We show here that increased activation of the HIF pathway, either through deletion of the negative regulator of HIF, the von Hippel-Lindau (VHL) gene, in myeloid cells, or through pharmacological inhibitors of VHL-mediated degradation of HIF, potently suppresses T cell proliferation in myeloid cell/T cell culture. These data demonstrate that both pharmacological and genetic activation of HIF in myeloid cells can suppress adaptive cell immune response.
髓系细胞与适应性免疫系统细胞的相互作用是免疫的一个重要方面。这种相互关系的一个关键方面是其受微环境的调节。众所周知，氧气会影响 T 细胞激活的骨髓抑制，部分原因是缺氧诱导（HIF）转录因子。目前有许多作用于 HIF 途径的药物在临床应用中，评估它们如何作用于免疫细胞功能非常重要，这是更好地了解它们将如何影响患者结局的一部分。我们在这里表明，通过髓系细胞中 HIF 负调节剂 von Hippel-Lindau（VHL）基因的缺失，或通过 VHL 介导的 HIF 降解的药理学抑制剂，增加 HIF 途径的激活，强烈抑制髓系细胞/T 细胞培养中的 T 细胞增殖。这些数据表明，髓系细胞中 HIF 的药理学和遗传学激活均可抑制适应性细胞免疫反应。
