Liang Lin, Hwang Ah-Reum, Guon Tae Eun, Park Kyung Hee, Park Chang Ook, Lee Jae-Hyun, Park Jung-Won
Graduate School of Medicine, Yonsei University College of Medicine, Seoul, Korea.
Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea.
Allergy Asthma Immunol Res. 2025 May;17(3):330-348. doi: 10.4168/aair.2025.17.3.330.
Gliadins are the primary triggers in wheat-dependent exercise-induced anaphylaxis. Currently, there are no officially approved immune-modulating treatments for gliadin allergy. Recent studies have shown that hyaluronic acid based dissolving microarray patch (dMAP) could deliver house dust mite allergens through transdermal pathway and protect allergic asthma and atopic dermatitis In this study, we explored the potential of dMAP for the transdermal delivery of gliadin proteins as a strategy to mitigate gliadin allergy.
C3H/HeJ mice were sensitized to gliadin with cholera toxin via oral administration, followed by oral or intraperitoneal gliadin challenge. To evaluate the protective effects of transdermal immunotherapy (TDIT), gliadin-loaded dMAPs were applied twice a week to gliadin-sensitized mice for 4 weeks. Afterward, the mice were challenged with gliadin.
The manufacturing process of dMAP did not alter the allergenicity of gliadin. TDIT significantly improved the anaphylaxis clinical score and stabilized core body temperature in the gliadin anaphylaxis model. It reduced mast cell protease-1 and gliadin-specific immunoglobulin E (IgE), and increased specific IgG₁, IgG and IgG levels. splenocyte study revealed that TDIT enhanced T helper type 1 (Th₁) cell population, interferon-γ expression, regulatory T cell population, and interleukin (IL)-10 expression, as well as suppressed Th₂ cell population and associated cytokines (IL-4, IL-5, and IL-13). Furthermore, this TDIT preserved the structural integrity of small intestinal villi and reduced eosinophil and mast cell infiltration.
Gliadin TDIT using dMAP mitigates gliadin-induced anaphylaxis in a murine model, offering a promising novel immune modulating treatment for gliadin-induced anaphylaxis.
麦醇溶蛋白是小麦依赖运动诱发过敏反应的主要触发因素。目前，尚无官方批准的针对麦醇溶蛋白过敏的免疫调节治疗方法。最近的研究表明，基于透明质酸的溶蚀性微阵列贴片（dMAP）可通过经皮途径递送屋尘螨过敏原，并对过敏性哮喘和特应性皮炎起到保护作用。在本研究中，我们探索了dMAP经皮递送麦醇溶蛋白的潜力，作为减轻麦醇溶蛋白过敏的一种策略。
通过口服给予霍乱毒素使C3H/HeJ小鼠对麦醇溶蛋白致敏，随后进行口服或腹腔注射麦醇溶蛋白激发。为了评估经皮免疫疗法（TDIT）的保护作用，每周两次将负载麦醇溶蛋白的dMAP应用于对麦醇溶蛋白致敏的小鼠，持续4周。之后，用麦醇溶蛋白对小鼠进行激发。
dMAP的制造过程未改变麦醇溶蛋白的致敏性。TDIT显著改善了麦醇溶蛋白过敏模型中的过敏反应临床评分并稳定了核心体温。它降低了肥大细胞蛋白酶-1和麦醇溶蛋白特异性免疫球蛋白E（IgE），并增加了特异性IgG₁、IgG和IgG水平。脾细胞研究表明，TDIT增强了1型辅助性T细胞（Th₁）群体、干扰素-γ表达、调节性T细胞群体和白细胞介素（IL）-10表达，同时抑制了Th₂细胞群体及相关细胞因子（IL-4、IL-5和IL-13）。此外，这种TDIT保留了小肠绒毛的结构完整性，并减少了嗜酸性粒细胞和肥大细胞浸润。
使用dMAP的麦醇溶蛋白TDIT可减轻小鼠模型中麦醇溶蛋白诱导的过敏反应，为麦醇溶蛋白诱导的过敏反应提供了一种有前景的新型免疫调节治疗方法。
