Tight junction and cell surface proteins cleaved by Dermatophagoides pteronyssinus allergen 1 (Der p 1)

Tight junction and cell surface proteins cleaved by Der p 1 represent a critical group of molecular targets involved in the pathogenesis of allergic diseases. Der p 1, a major cysteine protease allergen from house dust mites, directly degrades epithelial junctional proteins such as occludin, claudin-1, and zonula occludens-1 (ZO-1), thereby increasing the permeability of the airway epithelium to allergens and pathogens (Wan et al., 1999, PubMed: 10491416). Beyond physical barrier disruption, Der p 1 cleaves essential immune receptors including CD23 (FceRII) and CD25 (IL-2 receptor alpha), which promotes IgE synthesis and skews T-cell differentiation toward a pro-inflammatory Th2 phenotype (Schulz et al., 1998, PubMed: 9754565; Ghaemmaghami et al., 2002, PubMed: 11859111). This dual action of compromising structural integrity and dysregulating immune signaling makes these proteins central to the development of asthma and atopic dermatitis. While no drugs are currently approved to specifically protect these substrates, experimental cysteine protease inhibitors are being explored to prevent Der p 1-mediated damage. Understanding the specific cleavage sites and the resulting biological consequences is vital for developing targeted therapies to restore barrier function and immune homeostasis. Additionally, the cleavage of desmoglein-2 and CD40 further exacerbates tissue damage and immune activation in the respiratory tract. Monitoring the levels of soluble cleavage products like sCD23 or sCD25 may serve as biomarkers for allergen-induced protease activity in patients.

Other names

OccludinZonula occludens-1 (ZO-1)Claudin-1Desmoglein-2Low-affinity immunoglobulin epsilon Fc receptor (CD23)Interleukin-2 receptor subunit alpha (CD25)CD40 antigenDC-SIGNEpithelial barrier proteinsDer p 1 substrates

Proteolytic degradation of junctional and regulatory proteins by Der p 1, leading to barrier dysfunction and Th2-mediated inflammation.