FcγRIIb Inhibits Allergic Lung Inflammation in a Murine Model of Allergic Asthma
نویسندگان
چکیده
Allergic asthma is characterized by airway eosinophilia, increased mucin production and allergen-specific IgE. Fc gamma receptor IIb (FcgammaRIIb), an inhibitory IgG receptor, has recently emerged as a negative regulator of allergic diseases like anaphylaxis and allergic rhinitis. However, no studies to date have evaluated its role in allergic asthma. Our main objective was to study the role of FcgammaRIIb in allergic lung inflammation. We used a murine model of allergic airway inflammation. Inflammation was quantified by BAL inflammatory cells and airway mucin production. FcgammaRIIb expression was measured by qPCR and flow cytometry and the cytokines were quantified by ELISA. Compared to wild type animals, FcgammaRIIb deficient mice mount a vigorous allergic lung inflammation characterized by increased bronchoalveolar lavage fluid cellularity, eosinophilia and mucin content upon ragweed extract (RWE) challenge. RWE challenge in sensitized mice upregulated FcgammaRIIb in the lungs. Disruption of IFN-gamma gene abrogated this upregulation. Treatment of naïve mice with the Th1-inducing agent CpG DNA increased FcgammaRIIb expression in the lungs. Furthermore, treatment of sensitized mice with CpG DNA prior to RWE challenge induced greater upregulation of FcgammaRIIb than RWE challenge alone. These observations indicated that RWE challenge upregulated FcgammaRIIb in the lungs by IFN-gamma- and Th1-dependent mechanisms. RWE challenge upregulated FcgammaRIIb on pulmonary CD14+/MHC II+ mononuclear cells and CD11c+ cells. FcgammaRIIb deficient mice also exhibited an exaggerated RWE-specific IgE response upon sensitization when compared to wild type mice. We propose that FcgammaRIIb physiologically regulates allergic airway inflammation by two mechanisms: 1) allergen challenge mediates upregulation of FcgammaRIIb on pulmonary CD14+/MHC II+ mononuclear cells and CD11c+ cells by an IFN-gamma dependent mechanism; and 2) by attenuating the allergen specific IgE response during sensitization. Thus, stimulating FcgammaRIIb may be a therapeutic strategy in allergic airway disorders.
منابع مشابه
Study of Chenopodium Album Allergenic Extract to Induce Allergic Asthma in Murine Model
Background: The incidence of allergic and asthmatic diseases has been continuously increased in both industrial and developing countries. Extracts from various known allergens are used for the diagnostic and therapeutic purposes. Objective: To investigate the effects of an extract prepared from Chenopodium album (Ch.A.) pollen to induce allergic asthma in BALB/C mice. Methods: BALB/C mice were ...
متن کاملInactivated Mycobacterium phlei inhalation ameliorates allergic asthma through modulating the balance of CD4+CD25+ regulatory T and Th17 cells in mice
Objective(s): Th2 response is related to the aetiology of asthma, but the underlying mechanism is unclear. To address this point, the effect of nebulized inhalation of inactivated Mycobacterium phlei on modulation of asthmatic airway inflammation was investigated. Materials and Methods: 24 male BALB/c mice were randomly divided into three groups: control group (Group A), asthma model group (G...
متن کامل5-BDBD ameliorates an OVA-induced allergic asthma by the reduction of Th2 cytokines production
Objective(s): P2X4R is expressed in immunocyte and lung tissues. It has been a focus in inflammatory responses recently. This study investigated whether blockage of P2X4R attenuates allergic inflammation by modulating T cell response in ovalbumin-sensitized mice. Materials and Methods: Ovalbumin was used to sensitize and challenge for a mouse model. Intranasal application of 5-BDBD, P2X4R antag...
متن کاملThe effects of bone marrow-derived mesenchymal stem cells on ovalbumin-induced allergic asthma and cytokine responses in mice
Objective(s): Allergic Asthma is an inflammatory disease of the lungs that is characterized by increased infiltration of leukocytes into the airways, limiting the respiratory function. Studies suggest that a defective general regulatory system against inflammation could be a significant factor in allergic asthma. It has been shown that Mesenchymal stem cells (MSCs) have a cellular immunosuppres...
متن کاملSerum Level of Selenium, IL-4, IL-10 & IFN-g in Patients with Allergic Asthma, Allergic Rhinitis and Healthy Controls
Background: Allergic diseases have increased during the past decade worldwide. Th2 type lymphocyte response is known to play an important role in the process of allergic inflammation. IL-4, a mediator of type II cytokine response increases IgE synthesis and Interferon gamma, a cytokine of type I response interferes with IL-4 and inhibits IgE production. Selenium is an essential component of glu...
متن کامل