Hypoxia-inducible factor (HIF) prolyl-hydroxylase inhibitors are currently used for the treatment of renal anemia. Since HIF affects immune cells, we evaluated the effect of such a drug, the roxadustat, on adaptive immunity. Cell proliferation was assessed in a two-way mixed lymphocyte reaction (MLR) with BrdU assay. In CD4⁺ T cells isolated from the two-way MLRs, western blotting was performed to detect the impact of roxadustat on HIF-1α and HIF-2α, the apoptotic marker cleaved caspase-3, and the master transcription factors of CD4⁺ T cells differentiation towards Th1, Th2, Th17, Treg and Tfh subsets. The signature cytokines of the above CD4⁺ T-cell subsets IFN-γ, IL-4, IL-17, IL-10, and IL-21 were measured in the supernatants. For assessing humoral immunity, we developed a suitable antibody-mediated complement-dependent cytotoxicity assay. Roxadustat stabilized HIF-1α and HIF-2α, suppressed cell proliferation, inhibited CD4⁺ T-cell differentiation into Th1 and Th17 subsets, while it favored differentiation towards Th2, Treg and Tfh. Roxadustat suppressed humoral immunity too. These immunosuppressive properties of roxadustat indicate that the recently introduced HIF prolyl-hydroxylase inhibitors in medical therapeutics may render the patients vulnerable to infections. This possibility should be further evaluated in clinical trials.

缺氧诱导因子（HIF）脯氨酰羟化酶抑制剂目前用于治疗肾性贫血。由于 HIF 影响免疫细胞，我们评估了这种药物罗沙司他对适应性免疫的影响。用 BrdU 测定在双向混合淋巴细胞反应 (MLR) 中评估细胞增殖。在从双向 MLR 分离的CD4 ⁺ T 细胞中，进行蛋白质印迹以检测罗沙司他对 HIF-1α 和 HIF-2α、凋亡标志物切割 caspase-3 和 CD4 ⁺ T 细胞的主转录因子的影响分化为 Th1、Th2、Th17、Treg 和 Tfh 亚群。上述 CD4 ⁺的标志性细胞因子在上清液中测量 T 细胞亚群 IFN-γ、IL-4、IL-17、IL-10 和 IL-21。为了评估体液免疫，我们开发了一种合适的抗体介导的补体依赖性细胞毒性试验。Roxadustat 稳定 HIF-1α 和 HIF-2α，抑制细胞增殖，抑制 CD4 ⁺ T 细胞分化为 Th1 和 Th17 亚群，同时它有利于向 Th2、Treg 和 Tfh 分化。罗沙司他也抑制了体液免疫。罗沙司他的这些免疫抑制特性表明，最近在医学治疗中引入的 HIF 脯氨酰羟化酶抑制剂可能会使患者容易受到感染。这种可能性应在临床试验中进一步评估。