The house dust mite is the most common cause of allergic diseases, and TLR4 acts as an overarching receptor for allergic responses. This study aimed to identify novel allergen binding to TLR4 in house dust mites and unveil its unique role in allergic responses. Der p 38 was purified and characterized by liquid chromatography tandem mass spectrometry–based peptide mapping. Biolayer interferometry and structure modeling unveiled TLR4-binding activity and the structure of recombinant Der p 38. The allergenicity of Der p 38 was confirmed by a skin prick test, and basophil activation and dot blot assays. The skin prick test identified 24 out of 45 allergic subjects (53.3%) as Der p 38⁺ subjects. Der p 38–augmented CD203c expression was noted in the basophils of Der p 38⁺ allergic subjects. In animal experiments with wild-type and TLR4 knockout BALB/c mice, Der p 38 administration induced the infiltration of neutrophils as well as eosinophils and exhibited clinical features similar to asthma via TLR4 activation. Persistent Der p 38 administration induced severe neutrophil inflammation. Der p 38 directly suppressed the apoptosis of allergic neutrophils and eosinophils, and enhanced cytokine production in human bronchial epithelial cells, inhibiting neutrophil apoptosis. The mechanisms involved TLR4, LYN, PI3K, AKT, ERK, and NF-κB. These findings may contribute to a deep understanding of Der p 38 as a bridge allergen between eosinophilic and neutrophilic inflammation in the pathogenic mechanisms of allergy.

屋尘螨是过敏性疾病的最常见原因，TLR4 是过敏反应的主要受体。本研究旨在鉴定屋尘螨中与 TLR4 结合的新型过敏原，并揭示其在过敏反应中的独特作用。Der p 38 通过基于液相色谱串联质谱的肽图谱进行纯化和表征。生物层干涉仪和结构建模揭示了 TLR4 结合活性和重组 Der p 38 的结构。 Der p 38 的过敏性通过皮肤点刺试验、嗜碱性粒细胞活化和斑点印迹分析得到证实。皮肤点刺试验将 45 名过敏受试者中的 24 名 (53.3%) 鉴定为 Der p 38 ⁺受试者。在 Der p 38 ⁺的嗜碱性粒细胞中发现了 Der p 38 增强的 CD203c 表达过敏对象。在野生型和 TLR4 敲除 BALB/c 小鼠的动物实验中，Der p 38 给药诱导嗜中性粒细胞和嗜酸性粒细胞浸润，并通过 TLR4 激活表现出类似于哮喘的临床特征。持续的 Der p 38 给药诱导严重的中性粒细胞炎症。Der p 38 直接抑制过敏性中性粒细胞和嗜酸性粒细胞的凋亡，增强人支气管上皮细胞的细胞因子产生，抑制中性粒细胞凋亡。其机制涉及 TLR4、LYN、PI3K、AKT、ERK 和 NF-κB。这些发现可能有助于深入了解 Der p 38 作为过敏致病机制中嗜酸性粒细胞和中性粒细胞炎症之间的桥梁过敏原。