Sublingual Immunotherapy: How Sublingual Allergen Administration Heals Allergic Diseases; Current Perspective about the Mode of Action.

Owing to the successful application of sublingual immunotherapy (SLIT), allergen immunotherapy (AIT) has become one of the leading treatments for allergic diseases. Similar to the case with other AITs, such as subcutaneous and oral immunotherapies, not only the alleviation of allergic symptoms, but also the curing of the diseases can be expected in patients undergoing SLIT. However, how and why such strong efficacy is obtained by SLIT, in which allergens are simply administered under the tongue, is not clearly known. Various potential mechanisms, including the induction of blocking antibodies, T cell tolerance, regulatory B and T cells, CD103-CD11b+ classical dendritic cells, and CD206+ macrophages, and the reduction of innate lymphoid cells, mast cells, and basophils, have been suggested. Recently, through a comparative analysis between high- and non-responder patients of SLIT, we have successfully proposed several novel mechanisms. Here, we introduce our recent findings and summarize the current understanding of the mechanisms underlying the strong efficacy of SLIT.