Biodiversity Interventions for Well-being, Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland.
Cytokine Biology Research Group, Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland; Fimlab Laboratories, 33520 Tampere, Finland.
Cytokine. 2023 Apr;164:156159. doi: 10.1016/j.cyto.2023.156159. Epub 2023 Feb 19.
Interleukin (IL)-4 and IL-13 are related cytokines with well-known specific roles in type 2 immune response. However, their effects on neutrophils are not completely understood. For this, we studied human primary neutrophil responses to IL-4 and IL-13. Neutrophils are dose-dependently responsive to both IL-4 and IL-13 as indicated by signal transducer and activator of transcription 6 (STAT6) phosphorylation upon stimulation, with IL-4 being more potent inducer of STAT6. IL-4-, IL-13- and Interferon (IFN)-γ-stimulated gene expression in highly purified human neutrophils induced both overlapping and unique gene expression in highly purified human neutrophils. IL-4 and IL-13 specifically regulate several immune-related genes, including IL-10, tumor necrosis factor (TNF) and leukemia inhibitory factor (LIF), while type1 immune response-related IFN-γ induced gene expression related for example, to intracellular infections. In analysis of neutrophil metabolic responses, oxygen independent glycolysis was specifically regulated by IL-4, but not by IL-13 or IFN-γ, suggesting specific role for type I IL-4 receptor in this process. Our results provide a comprehensive analysis of IL-4, IL-13 and IFN-γ -induced gene expression in neutrophils while also addressing cytokine-mediated metabolic changes in neutrophils.
白细胞介素 (IL)-4 和 IL-13 是相关的细胞因子，在 2 型免疫反应中具有明确的特定作用。然而，它们对中性粒细胞的影响尚未完全阐明。为此，我们研究了人原代中性粒细胞对 IL-4 和 IL-13 的反应。中性粒细胞对 IL-4 和 IL-13 的反应呈剂量依赖性，表现为刺激后信号转导和转录激活因子 6（STAT6）磷酸化，其中 IL-4 是更有效的 STAT6 诱导剂。IL-4、IL-13 和干扰素 (IFN)-γ 刺激高度纯化的人中性粒细胞中的基因表达，诱导高度纯化的人中性粒细胞中重叠和独特的基因表达。IL-4 和 IL-13 特异性调节几种免疫相关基因，包括 IL-10、肿瘤坏死因子 (TNF) 和白血病抑制因子 (LIF)，而 1 型免疫反应相关的 IFN-γ 诱导的基因表达与例如细胞内感染有关。在中性粒细胞代谢反应分析中，IL-4 特异性调节非依赖氧的糖酵解，但 IL-13 或 IFN-γ 则没有，这表明 I 型 IL-4 受体在该过程中具有特定作用。我们的研究结果提供了对中性粒细胞中 IL-4、IL-13 和 IFN-γ 诱导的基因表达的全面分析，同时还解决了细胞因子介导的中性粒细胞代谢变化。
