Immune mechanisms induced by sublingual immunotherapy in allergic respiratory diseases

Abstract

Allergic respiratory diseases (ARDs) are still a major burden on global public health. Sublingual immunotherapy (SLIT) is a mode of allergen immunotherapy (AIT) which involves administration of the allergen under the tongue, and benefits from tolerogenic properties of the oral mucosa. Studies revealed reduced levels of eosinophilia and eosinophil-dominated inflammation in airways of both animals and humans after SLIT. SLIT was also suggested to lower basophil responsiveness and innate lymphoid cell-2 function in blood samples collected from patients with ARD. Moreover, apart from shifting pathogenic type 2 (TH2) to a type 1 (TH1) and protective regulatory (Treg) polarization of helper T-cell immune response, antibody isotype switch from IgE to IgG1, IgG2, IgG4 and IgA was also reported in patients with ARD receiving SLIT. Today, the literature on SLIT-mediated activities is still scarce and more studies are required to further enlighten the mechanisms utilized by SLIT for the induction of tolerance. The aim of this review is to summarize the current knowledge about the immune-regulatory mechanisms induced by SLIT against ARDs.

Keywords: SLIT; adaptive; allergic respiratory diseases; immune response; innate.

Figure 1:

immune-regulatory mechanisms demonstrated for SLIT against ARDs. Both animal and human studies reported reduced level of respiratory eosinophilia and eosinophil-dominated inflammation (a). The SLIT was also suggested to exert inhibitory activities on blood basophil responsiveness (b) and ILC2 function (c) in patients with ARD. Animal studies suggested the positive contribution of facilitating antigen uptake by DCs to increase SLIT activity against ARDs (d). Treg differentiation in response to SLIT is supported by oral macrophage-like cells migrating to cervical lymph nodes (e). The SLIT induced an adaptive immune response toward a T_H1 and Treg, phenotype away from the allergic T_H2 phenotype, in both animal and human patient studies using blood samples (f). In correlation with the skewed T-cell-mediated immune response, the SLIT was also associated with serum antibody isotype switch from IgE to IgG1, IgG2, and IgG4 in patients with ARD (g). The lack of change in serum IgA levels were suggested to be due to enhanced transportation of IgA into the mucosal secretions (h). The figure was generated using BioRender software.