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Japanese cedar pollinosis (JCP) is a specific seasonal allergic disease which affects ~30% of the Japanese population, between February and April, every year.1 Apart from a series of symptomreliever medications, allergen-specific immunotherapy (AIT) is one of the most effective treatments for JCP. After several years of relying on the application of subcutaneous immunotherapy (SCIT) with standardized Japanese cedar pollen extract (since the 1960s), the use of sublingual immunotherapy (SLIT) was approved in 2014.2 In addition to the numerous clinical and scientific evidences pertaining to its effectiveness and safety on JCP including the results of randomized, placebo-controlled, double-blind studies,3,4 SLIT is also easier to administer and safer than SCIT, in which a systemic allergen injection is required and severe side effects include fatal anaphylaxis. However, the underlying mechanisms through which SLIT and SCIT exhibit their efficacy have not been fully elucidated. Despite the usefulness of SLIT, it has been reported that approximately 30% of JCP patients do not respond to this therapy.4,5 Dividing patients into high-responder (HR) and non-responder (NR) groups could be helpful in understanding the mechanisms of SLIT. We recently performed a clinical study of SLIT with cedar pollen extract on 193 adult patients with JCP.5 Among 142 patients who completed 2 years of SLIT, 102 (72%) showedmore than 1 level of improvement in the severity score. Regardless of whether they improved due to a placebo effect, we selected the top 33 HR patients in order of improvement rank.5 The bottom 34 NR patients were also selected, and their serum factors were comparatively analyzed before and after SLIT. Although the HR and NR groups were not distinguishable by any single parameter, they could be clearly separated by processing the parameters with an ensemble algorithm, Adaptive Boosting.5 We also analyzed the population of peripheral blood CD4þ T cells, basophils, conventional dendritic cells, and plasmacytoid dendritic cells.5 Although there were no significant differences in these populations, between the HR and NR groups, CD4þ T cells are implicated in the effect of AIT.6 In addition, by using cluster analysis for all serum parameters, we found that the presence of specific cytokines for Th1 and Th2 cell subsets was strongly correlatedwith HR but not NR patients in our previous study.5 Therefore, comparative genome-wide transcriptome analyses with CD4þ T cell mRNA, isolated from the HR and NR patients, were performed herein. After the exclusion of samples of cypress pollen-specific IgE-positive patients and samples in which the

Involvement of taste receptors in the effectiveness of sublingual immunotherapy