Semaphorin 7A plays a critical role in IgE-mediated airway inflammation in mice

Elevated allergen-specific IgE levels are a hallmark of allergic asthma, a disease involving chronic airway inflammation characterized by airway hyperresponsiveness (AHR); neutrophilic airway inflammation is Found in patients with severe asthma. Furthermore, we have reported that interleukin (IL)-33 and IL-17A contribute to IgE-mediated AHR through neutrophilic inflammation in mice. Meanwhile, semaphorins regulating neuronal and immune function have been focused on in several diseases. Here, we investigated whether semaphorin 7A (SEMA7A) is related to IgE-mediated neutrophilic inflammation in mice. BALB/c mice sensitized with antigen-specific IgE monoclonal antibody were repeatedly challenged by the antigen. When anti-SEMA7A antibody was administered during the fourth to seventh challenges, the infiltration by macrophages, lymphocytes, neutrophils, and cosinophils in the lungs was reduced at the seventh challenge (P < 0.05, 0.05, 0.01, and 0.05, respectively). However, the increased production of IL-4, IL-5, IL-13, IL-33, IL-17A, IL-6, and CXCL1 in the lungs was not suppressed. In histological analysis, the epithelial cells, blood vessels, and inflammatory cells in the lungs of IgE-sensitized mice showed SEMA7A expression; plexin C1 for the receptor was expressed in the inflammatory cells. Meanwhile, we examined the effect of anti-SEMA7A antibody on AHR and neutrophilic inflammation enhanced by the collaborative action of IL-33 and IL-17A in normal mice, resulting in the suppression of these responses (P < 0.05 and 0.01, respectively). Collectively, we demonstrated that SEMA7A plays a critical role in IgE-mediated neutrophilic airway inflammation. Therefore, SEMA7A may be a potential therapeutic target for severe allergic asthma showing neutrophilic airway inflammation. (C) 2015 Elsevier B.V. All rights reserved.