Purpose. Vitamin D (VitD) deficiency is a significant public health concern in many areas around the globe and has been associated with many immune-mediated diseases, including asthma. Severe asthma has been linked to a decreased glucocorticoid receptor (GR) ratio (GR-α/GR-β ratio), indicating steroid hyporesponsiveness. Using a combination of in silico and in vivo approaches, we aimed to explore the immunomodulatory effect of VitD on asthmatic patients diagnosed with hypovitaminosis D. Methods. In silico tools were used to identify the regulatory effect of VitD supplementation on GR genes. We measured the expression levels of GR-α and the inactive isoform, GR-β, in the blood of adult asthmatics diagnosed with hypovitaminosis D before and after VitD supplementation. Moreover, the blood levels of inflammatory cytokines associated with asthma severity were determined. Results. Using an in silico approach, we identified specific genes commonly targeted by VitD as well as corticosteroids, the mainstay of asthma therapy. NR3C1 gene encoding GR was found to be significantly upregulated on Th2 CD4 cells and NK cells. Interestingly, blood expression level of NR3C1 was lower in severe asthmatics compared to nonsevere asthmatics and healthy controls, while the blood level of VitD receptor (VDR) was higher. Upon VitD supplementation of severe asthmatic patients, there was a significant increase in the blood levels of GR-α with no change in GR-β mRNA expression. VitD supplementation also suppressed the blood levels of IL-17F and IL-4. Conclusion. VitD may enhance steroid responsiveness by upregulating the expression of steroid receptor GR-α.

中文翻译：

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维生素 D 调节重症哮喘患者血液中糖皮质激素受体的表达

目的。维生素 D (VitD) 缺乏是全球许多地区的一个重大公共卫生问题，并且与许多免疫介导的疾病有关，包括哮喘。严重哮喘与降低的糖皮质激素受体 (GR) 比率（GR -α / GR- β比率）有关，表明类固醇低反应性。使用计算机和体内方法的组合，我们旨在探索 VitD 对诊断为维生素缺乏症 D 的哮喘患者的免疫调节作用。方法。计算机工具用于确定补充 VitD 对 GR 基因的调节作用。我们测量了 GR -α的表达水平以及在补充 VitD 前后诊断为维生素 D 缺乏症的成年哮喘患者血液中的非活性同工型 GR - β 。此外，测定了与哮喘严重程度相关的炎性细胞因子的血液水平。结果。使用计算机通过方法，我们确定了 VitD 和皮质类固醇通常靶向的特定基因，皮质类固醇是哮喘治疗的支柱。发现编码 GR 的 NR3C1 基因在 Th2 CD4 细胞和 NK 细胞上显着上调。有趣的是，与非重症哮喘患者和健康对照组相比，重症哮喘患者的 NR3C1 血液表达水平较低，而 VitD 受体 (VDR) 的血液表达水平较高。对严重哮喘患者补充 VitD 后，GR -α的血液水平显着增加，而 GR- β mRNA 表达没有变化。VitD 补充剂还抑制了 IL-17F 和 IL-4 的血液水平。结论。VitD 可能通过上调类固醇受体 GR -α的表达来增强类固醇反应性.