Mucosal immunity and sublingual immunotherapy in respiratory disorders

The increasing prevalence of allergy and its impact on individual quality of life underline the need of an improvement of the treatment options in order to modify the natural course of allergic diseases. In this context, specific sublingual immunotherapy (SLIT) represents an approach currently available to redirect inappropriate immune response in atopic patients. The immunological mechanism that underlies SLIT has only started to be investigated. Oral mucosal tissue displays high permeability for allergens. It is conceivable that the sublingual administration route might induce immunological tolerance towards allergens involving cells and mediators specific of oral and intestinal mucosa. Recent literature data stated the presence in oral mucosa of dendritic cells (DCs) which express the high-affinity receptor for immunoglobulin (Ig)E (FcERI). Moreover some studies indicated that the mechanism of immunotherapy might be based on the increase of number and activity of regulatory T cells. Accumulating evidences suggest that the generation of T regulatory cells in periphery is orchestrated by a particular subset of DCs. It seems that repeated stimulation of naive CD4 T cells with allogenic immature DCs induce Tr1 cells maturation. Nevertheless other cells are involved in this process, such as TLR, MHC of I and II class and costimolatory molecules such as CD40, CD 80/B7.1 and CD 86/B7.2. An increase of serum IgG4 and IgA, a reduced number of inflammatory cells infiltrating target organs, as well as a reduction of eosinophilic cationic protein and a very heterogenous influence on T cells in the peripheral blood in terms of T cell suppression also occur with SLIT. All these molecules orchestrate the immune response within the regional immune system, recreating a favourite environment for the induction of tolerance operated by SLIT.