Long-Lasting Effect of Allergen-Specific Sublingual Immunotherapy in a Murine Model of Japanese Cedar Pollinosis

Sublingual immunotherapy (SLIT) is considered a potentially curative treatment for allergic diseases, but the mechanism remains to be elucidated. Japanese cedar (JC) pollen, which is dispersed in early spring, is a major cause of allergic rhinitis in Japan. We established a murine model of JC pollinosis and evaluated the effect of JC pollen extract SLIT. BALB/c mice were intranasally sensitized to JC pollen, then administered four courses of nasal allergen challenge at 5-week intervals, mimicking seasonal JC pollen exposure. Between allergen challenges, mice were treated sublingually with two doses (low or high) of JC pollen extract. Mice received no SLIT treatment between the third and fourth challenges to allow assessment of long-term effects. Nasal symptoms, T-cell response, antibodies, and histological changes in nasal mucosa were examined. JC-SLIT significantly reduced the JC pollen-induced nasal symptoms, both during and approximately 2 months after SLIT treatment. While the magnitude of the effect at the end of SLIT was similar in the low- and high-dose groups, the high-dose group showed a greater effect in the off-treatment period, suggesting more potent lasting effects with higher SLIT doses. Th2 cytokine production in submandibular lymph nodes, nasal mucosa hyperplasia, and JC-specific IgE were reduced in the JC-SLIT-treated groups. We have developed a JC pollinosis mouse model that may be useful for studying SLIT mechanisms and biomarkers. Our results also demonstrate that SLIT induces long-lasting effects, which occur in a dose-dependent manner.