Mechanisms and regulators of upper respiratory allergic disease

<p>Eosinophilic rhinosinusitis and allergic rhinitis are typical eosinophilic and allergic inflammatory diseases of the upper respiratory tract.</p><p>Eosinophilic rhinosinusitis is often recurrent even after surgery and is treated as a refractory disease. Moreover, eosinophilic sinusitis is known to be strongly associated with the innate immune response that induces type 2 inflammation without antigen sensitization. Epithelial-derived cytokines (TSLP, IL-25, IL-33) produced by epithelial cells are thought to induce large amounts of type 2 cytokine production via type 2 innate lymphoid cells (ILC2) and pathogenic memory Th2 cells, forming the characteristic histology of eosinophilic rhinosinusitis, including eosinophil infiltration, mucin production, and goblet cell hyperplasia.</p><p>Allergic rhinitis is a disease that affects almost half of the Japanese population. Allergen immunotherapy (AIT) has been shown to be highly effective in treating allergic rhinitis and is the only method that can be expected to provide long-term remission and cure. The mechanism of action of AIT is based on inducing immunological tolerance characterized by increased IL-10, TGF-β, and IgG4 levels and Treg cells. However, the mechanism by which AIT induces long-term remission has not been elucidated.</p><p>Both diseases are characterized by type 2 inflammation or IgE-dependent allergic inflammation, and managing these inflammations may lead to effective treatments.</p><p>This report describes the pathophysiology of eosinophilic chronic rhinosinusitis and novel mechanisms of AIT based on our studies.</p>