University of Groningen, University Medical Center Groningen, Department of Pathology & Medical Biology, Experimental Pulmonary and Inflammatory Research (EXPIRE), Groningen, The Netherlands.
Groningen Research Institute of Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Sci Rep. 2020 Jun 2;10(1):8960. doi: 10.1038/s41598-020-65946-6.
Allergen specific immunotherapy (AIT) can provide long-term alleviation of symptoms for allergic disease but is hampered by suboptimal efficiency. We and others have previously shown that 1,25(OH)2-VitaminD3 (VitD3) can improve therapeutic efficacy of AIT. However, it is unknown whether VitD3 supplementation has similar effects in sublingual and subcutaneous immunotherapy. Therefore, we aimed to test VitD3 supplementation in both grass pollen (GP) subcutaneous-IT (SCIT) and sublingual-IT (SLIT) in a mouse model for allergic airway inflammation. To this end, GP-sensitized BALB/c mice received GP-SCIT or GP-SLIT with or without 10 ng VitD3, followed by intranasal GP challenges and measurement of airway hyperresponsiveness (AHR) and inflammation. VitD3 supplementation of GP-SCIT resulted in enhanced induction of GP-specific (sp)-IgG2a and suppression of spIgE after challenge. In addition, eosinophil numbers were reduced and levels of IL10 and Amphiregulin were increased in lung tissue. In GP-SLIT, VitD3 supplementation resulted in enhanced sp-IgG2a levels in serum, enhanced suppression of eosinophils and increased IL10 levels in lung tissue, as well as suppression of AHR to methacholine. These data show that VitD3 increases efficacy of both SCIT and SLIT, by enhancing induction of blocking antibodies and suppression of airway inflammation, underscoring the relevance of proficient VitD3 levels for successful AIT.
过敏原特异性免疫疗法（AIT）可以为过敏性疾病提供长期的症状缓解，但疗效并不理想。我们和其他人之前已经表明，1,25(OH)2-维生素 D3（VitD3）可以提高 AIT 的治疗效果。然而，尚不清楚 VitD3 补充是否对舌下和皮下免疫疗法具有类似的作用。因此，我们旨在测试 VitD3 补充对草花粉（GP）皮下免疫疗法（SCIT）和舌下免疫疗法（SLIT）在过敏性气道炎症的小鼠模型中的作用。为此，我们用 GP 致敏 BALB/c 小鼠，接受含有或不含有 10ng VitD3 的 GP-SCIT 或 GP-SLIT 治疗，然后进行鼻内 GP 挑战，并测量气道高反应性（AHR）和炎症。GP-SCIT 中 VitD3 的补充导致挑战后 GP 特异性（sp）-IgG2a 的诱导增强和 spIgE 的抑制。此外，肺组织中嗜酸性粒细胞数量减少，IL10 和 Amphiregulin 的水平增加。在 GP-SLIT 中，VitD3 补充导致血清中 sp-IgG2a 水平升高，对嗜酸性粒细胞的抑制增强，肺组织中 IL10 水平增加，以及对乙酰甲胆碱的 AHR 抑制。这些数据表明，VitD3 通过增强阻断抗体的诱导和抑制气道炎症，提高了 SCIT 和 SLIT 的疗效，强调了 VitD3 水平的充足对成功的 AIT 的重要性。
