title: Prevention and treatment of allergic inflammation by an Fcγ-Der f2 fusion protein in a murine model of dust mite-induced asthma.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, People's Republic of China.
authors.forename: Li-hui
authors.initials: LH
authors.lastname: Lin
authors.forename: Ping
authors.initials: P
authors.lastname: Zheng
authors.forename: John W M
authors.initials: JW
authors.lastname: Yuen
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.forename: Cun-quan
authors.initials: CQ
authors.lastname: Kong
authors.forename: Xia
authors.initials: X
authors.lastname: Peng
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D060829:Arthropod Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002681:China; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D040001:Dermatophagoides farinae / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D016207:Cytokines; C451160:Dermatophagoides farinae antigen f 2; C499172:Fcgr2b protein, mouse; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins