Inflammation in Respiratory Allergy Treated by Sublingual Immunotherapy

Abstract

The most common allergic diseases, such as rhinitis, asthma and atopic dermatitis, are sustained by allergic inflammation, the treatment of which requires anti-inflammatory activity. Among the available treatments, allergen immunotherapy (IT) has a documented impact on allergic inflammation which persists after its discontinuation and modifies the natural course of allergy. The anti-inflammatory effects of IT, and particularly of sublingual IT (SLIT), are based on the ability to modify the phenotype of T cells which, in allergic subjects, are characterized by a prevalence of the Th2 type, with production of IL-4, IL-5, IL-13, IL-17, and IL-32 cytokines. IT-induced changes result in a Th1-type response (immune deviation) related to an increased IFN-gamma and IL-2 production or in a Th2 reduced activity, through a mechanism of anergy or tolerance. It is now known that T cell tolerance is characterized by the generation of allergen-specific Treg cells, which produce cytokines such as IL-10 and TGF-beta with immunosuppressant and/or immunoregulatory activity. Recent studies suggest that the anti-inflammatory mechanism of SLIT is similar to classical, subcutaneous IT, with a prominent role in SLIT for mucosal dendritic cells. The tolerance pattern induced by Treg accounts for the suppressed or reduced activity of inflammatory cells and for the isotypic switch of antibody synthesis from IgE to IgG, and especially to IgG4. Data obtained from biopsies clearly indicate that the pathophysiology of the oral mucosa plays a pivotal role in inducing tolerance to the sublingually administered allergen.