Abstract
Abstract Japanese cedar (Cryptomeria japonica) pollinosis (JCP) is one of the most common allergic diseases in Japan. Sublingual immunotherapy (SLIT) has been performed as a safer and more beneficial treatment to induce allergen-specific immune tolerance. However, immunological mechanisms and therapeutic biomarkers for SLIT remain unclear. In this study, we have established a new murine model of JCP that resembles human JCP with crude pollen grains and without the use of adjuvant and examined the effects of SLIT. SLIT was performed by the graded doses of cedar pollen extract painting onto the ventral surface of tongue for 28 days. [Results] The frequency of sneezing and the duration of rubbing for 10 min after the final challenge, serum IgE titer, pollen-specific IgG1, and the ratio of eosinophils in BALF and nasal mucosae were significantly elevated in the pollinosis mice. SLIT efficiently reduced the above manifestations. SLIT significantly decreased pollen-specific IL-4, IL-5, IL-13 and IL-10 production by splenic T cells and DC activation status such as MHC class II, CD86, and B7-H1 expression in the regional lymph nodes. Histological examination revealed that repeated pollen extract painting onto the sublingual mucosae replaced sublingual resident DCs with newly recruited CD11b+ DCs. These results suggest that our new pollinosis model is beneficial to evaluate and develop a new immunotherapy and therapeutic biomarkers.
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