Modulation of airway inflammation by recombinant Der p 38 mutant immunotherapy in a murine model of allergic asthma

Asthma is a chronic allergic lung disease frequently triggered by exposure to house dust mites (HDM). Der p 38, an important allergen from Dermatophagoides pteronyssinus (DP), contributes mixed granulocytic asthma. However, the therapeutic potential of allergen immunotherapy (AIT) targeting Der p 38 remains unclear. Recombinant Der p 38 mutant proteins including D141A and PreS-2P5 were generated using molecular biology techniques. Although D141A retained TLR4-binding capacity, it did not affect neutrophil apoptosis or cytokine release in BEAS-2B cells. In mice, D141A induced weaker asthmatic responses than wild-type Der p 38 (WT), and co-administration of WT with D141A attenuated mixed granulocytic asthma features due to WT. AIT with WT, D141A, or the combination of D141A and PreS-2P5 suppressed Der p 38-induced mixed granulocytic asthma, and also reduced mixed granulocytic asthma due to persistent DP exposure. In neutrophilic asthma induced by chronic Der p 38 administration, AIT using D141A and PreS-2P5 markedly inhibited neutrophil infiltration, mucus production, and IgE, and enhanced specific IgG1/IgG2a in serum as well as IFN-γ and IL-10 in BALF, compared with other AIT groups. These findings suggest that Der p 38-based mutant protein and peptide are promising candidates for the treatment of diverse asthma endotypes and severities associated with HDM.