Effects of Local Nasal Immunotherapy with FIP-fve Peptide and Denatured Tyrophagus putrescentiae for Storage Mite-Induced Airway Inflammation

Abstract

Allergic diseases are affecting public health and have increased over the last decade. Sensitization to mite allergens is a considerable trigger for allergy development. Storage mite-Tyrophagus putrescentiae shows great significance of allergenic potential and clinical relevance. The fungal immunomodulatory peptide FIP-fve has been reported to possess immunomodulatory activity. We aimed to determine whether T. putrescentiae-induced sensitization and airway inflammation in mice could be downregulated by FIP-fve in conjunction with denatured T. putrescentiae (FIP-fve and DN-Tp). Immune responses and physiologic variations in immunoglobulins, leukocyte subpopulations, cytokine productions, pulmonary function, lung pathology, cytokines in CD4⁺ and Treg cells were evaluated after local nasal immunotherapy (LNIT). After the LNIT with FIP-fve and DN-Tp, levels of specific IgE, IgG1, and IgG2a in the sera and IgA in the bronchoalveolar lavage fluid (BALF) were significantly reduced. Infiltrations of inflammatory leukocytes (eosinophils, neutrophils, and lymphocytes) in the airway decreased significantly. Production of proinflammatory cytokines (IL-5, IL-13, IL-17F and IL-23) and chemokine (IL-8) were significantly reduced, and Th1-cytokine (IL-12) increased in the airway BALF after LNIT. Pulmonary functions of Penh values were significantly decreased after the methacholine challenge, which resulted in a reduction of airway hypersensitivity after LNIT. Bronchus pathology showed a reduction of inflammatory cell infiltration and epithelium damage after LNIT. The IL-4⁺/CD4⁺ T cells could be downregulated and the IFN-γ⁺/CD4⁺ T cells upregulated. The Treg-related immunity of IL-10 and Foxp3 expressions in CD4⁺CD25⁺ cells were both upregulated after LNIT. In conclusion, LNIT with FIP-fve and DN-Tp had an anti-inflammatory effect on mite-induced airway inflammations and possesses potential as an immunomodulatory therapy agent for allergic airway diseases.