Improvement of Therapeutic Efficacy of Oral Immunotherapy in Combination with Regulatory T Cell-Inducer Kakkonto in a Murine Food Allergy Model.
Improvement of Therapeutic Efficacy of Oral Immunotherapy in Combination with Regulatory T Cell-Inducer Kakkonto in a Murine Food Allergy Model.
复制标题
在鼠类食品过敏模型中，口服免疫疗法与调节性T细胞诱导剂Kakkonto结合使用的治疗功效提高。
DOI：
10.1371/journal.pone.0170577
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Kadowaki M
中科院分区：
文献类型：
--
作者：
Nagata Y;Yamamoto T;Hayashi M;Hayashi S;Kadowaki M
口服免疫疗法(OIT)被认为是治疗食物过敏(FAs)的一种有前途的方法。然而，目前的OIT策略在长期有效性和安全性方面是有限的。我们之前已经证明，日本传统草药葛根可以抑制卵蛋白(OVA)诱导的FA小鼠模型中过敏症状的发生，这归因于Foxp3+CD4+调节性T细胞的诱导。在这项研究中，我们使用已经有过敏症状的FA小鼠建立了OIT模型，并确定Kakkonto是否可以改善OIT的疗效。OIT方法包括最初给予非常少量的OVA，然后缓慢增加数量。OIT处理的FA小鼠过敏症状减轻。Oit显著下调FA小鼠结肠中Th2免疫反应相关基因的表达，并降低FA小鼠血浆中肥大细胞脱颗粒的标志物--小鼠肥大细胞蛋白酶-1的水平。此外，葛根素合用显著提高了OIT对过敏症状的疗效，联合治疗进一步抑制了Th2免疫反应和肥大细胞脱颗粒。此外，Oit显著增加FA小鼠结肠中Foxp3+CD4+调节性T细胞的数量，而Oit与kakkonto联合使用后，这一数量进一步增加。此外，葛根多联合治疗可降低FA小鼠结肠中RA降解酶CYP26B1mRNA的表达。这些发现表明，OIT和Kakkonto的结合是治疗FA的一种有前途的方法。
Oral immunotherapy (OIT) has been considered a promising approach for food allergies (FAs). However, the current OIT strategy is limited in terms of the long-term efficacy and safety. We have previously demonstrated that kakkonto, a traditional Japanese herbal medicine, suppresses the occurrence of allergic symptoms in a murine model of ovalbumin (OVA)-induced FA, which is attributed to the induction of the Foxp3+ CD4+ regulatory T cells. In this study, we established an OIT model using the FA mice with already established allergic symptoms and determined whether kakkonto could improve the efficacy of OIT. The OIT method consisted of initially administrating a very small amount of OVA and slowly increasing the amount. Allergic symptoms decreased in the OIT-treated FA mice. OIT significantly downregulated Th2 immune response-related gene expression in the FA mouse colon, and decreased the level of mouse mast cell protease-1, a marker of mast cell degranulation in the FA mouse plasma. Moreover, the concomitant use of kakkonto significantly enhanced the effectiveness of OIT on the allergic symptoms, and the combination therapy further suppressed the Th2 immune responses and the mast cell degranulation. In addition, OIT significantly increased the population of Foxp3+ CD4+ regulatory T cells in the FA mouse colon, and this population was further increased by OIT in combination with kakkonto. Furthermore, the combined therapy with kakkonto reduced the expression of RA-degrading enzyme CYP26B1 mRNA in the FA mouse colon. These findings indicated that the combination of OIT with kakkonto represents a promising approach for FA treatment.