Prevention and treatment of allergic inflammation by an Fcγ-Der f2 fusion protein in a murine model of dust mite-induced asthma

• Published in: Immunologic research 2012-06, Vol.52 (3), p.276-283
• Main Authors: Lin, Li-hui, Zheng, Ping, Yuen, John W. M., Wang, Juan, Zhou, Juan, Kong, Cun-quan, Peng, Xia, Li, Jia, Li, Li
• Format: Article
• Language: English
• Subjects: Allergic diseases; Allergology; Alveoli; Anaphylaxis; Animal models; Animals; Antigens, Dermatophagoides - genetics; Antigens, Dermatophagoides - immunology; Antigens, Dermatophagoides - pharmacology; Arthropod Proteins - genetics; Arthropod Proteins - immunology; Arthropod Proteins - pharmacology; Asthma; Asthma - drug therapy; Asthma - immunology; Asthma - metabolism; Asthma - pathology; Biomedical and Life Sciences; Biomedicine; Blood vessels; Bronchus; China; Cytokines - biosynthesis; Cytokines - immunology; Dermatophagoides farinae; Dermatophagoides farinae - immunology; Disease Models, Animal; Dust; Fc receptors; Female; Fusion protein; gamma -Interferon; Gene Expression Regulation - drug effects; Gene Expression Regulation - immunology; Helper cells; Histamine; Hypersensitivity; Immunoglobulin E; Immunology; Immunotherapy; Inflammation; Interleukin 10; Interleukin 12; Interleukin 18; Interleukin 4; Interleukin 5; Internal Medicine; Leukocytes (basophilic); Lymphocytes T; Mast cells; Medicine/Public Health; Mice; Mice, Inbred BALB C; Receptors, IgG; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; Recombinant Fusion Proteins - pharmacology; Respiratory tract; Th1 Cells - immunology; Th1 Cells - metabolism; Th1 Cells - pathology; Th2 Cells - immunology; Th2 Cells - metabolism; Th2 Cells - pathology; Tumor necrosis factor- alpha
• ISSN: 0257-277X; 1559-0755
• DOI: 10.1007/s12026-012-8339-x

The immunoglobulin E (IgE) high-affinity receptor FcεRI expressed on mast cells and basophils plays a critical role in triggering allergic disease. The co-aggregation of the FcεRI and FcγRIIb receptors is inhibitory to FcεRI signaling and holds great potential for the treatment of IgE-mediated allergies. In China, Dermatophagoides farinae is a common anaphylaxis trigger. Therefore, in this study, the FcγRIIb-mediated immunomodulating activity of recombinant Fcγ-Der f2 fusion protein was tested in a Der f2-allergic murine model. Following the treatment, bronchoalveolar lavage fluid (BALF) was collected to measure the expression of several Th1/Th2-type cytokines (IL-5, TNF-α, IL-12p70, IL-4, IL-10, IFN-γ and IL-18) and histamine, while blood was used to detect the specific IgE and IgG-types anti-Der f2 antibodies, for measurement. In contrast to the saline-treated allergic mice, the levels of Der f2-specific IgE, cytokines and histamine were lowered in the Fcγ-Der f2-treated allergic mice, in addition to the rare inflammatory cell infiltration in the airways and blood vessels revealed by histopathological examination. The recombinant Fcγ-Der f2 protein was demonstrated to function as an effective immunotherapeutic agent, suggesting that chimeric human Fcγ-allergen proteins could be used in the development of antigen-specific immunotherapy for human allergic diseases.