These results are useful for understanding the molecular basis of the mechanisms of CRSwNP and point to new targets for developing specific biomarkers and personalized therapeutic strategies for CRSwNP.

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BackgroundInterleukin-31 (IL-31) is a recently identified cytokine produced by Th2 cells that is involved in the development of atopic dermatitis-induced skin inflammation and pruritus. Its receptor, IL-31RA, is expressed by a number of cell types, including epithelial cells, eosinophils, and activated monocytes and macrophages. To date, however, the regulation of Th2 responses by distinct cell types and tissues expressing IL-31RA has not been well studied.MethodsIn this study, Cry j 2, one of the major allergens of Japanese cedar pollen, was administered to IL-31RA-deficient or wild-type (WT) mice via nasal or intraperitoneal injection for induction of specific Th2 responses.ResultsAfter nasal administration of Cry j 2, IL-31RA-deficient mice showed lower Cry j 2-specific CD4+ T cell proliferation, Th2 cytokine (IL-5 and IL-13) production, and Th2-mediated (IgE, IgG1, and IgG2b) antibody responses than WT mice. In contrast, IL-31RA-deficient mice administered Cry j 2 intraperitoneally showed stronger Th2 immune responses than WT mice.ConclusionsThese results indicate that IL-31R signaling positively regulates Th2 responses induced by nasal administration of Cry j 2, but negatively regulates these responses when Cry j 2 is administered intraperitoneally. Collectively, these data indicate that the induction of antigen-specific Th2 immune responses might depend on tissue-specific cell types expressing IL-31RA.

Background Japanese cedar (JC) pollinosis is a serious type I allergic disease in Japan. Although subcutaneous immunotherapy and sublingual immunotherapy have been applied to treat JC pollinosis, high doses of allergens may cause IgE-mediated allergic reactions. The transgenic rice seeds that contain genetically modified Cry j 1 and Cry j 2, the two major allergens of JC pollen, have been developed as candidates for oral immunotherapy. Although the antigens in the transgenic rice seeds (Tg-rice seeds) were engineered such that they decrease binding ability with IgE and they are of insufficient length to cross-link IgE on the surface of mast cells or basophils, the safety of Tg-rice seeds for patients with JC pollinosis was unclear. Methods To verify the safety of Tg-rice seeds in terms of allergies, we investigated the percentage of activated basophils induced by Tg-rice seed extract in the basophil activation test. Blood samples from 29 patients with JC pollinosis were collected. Tg-rice seed extract, non-transgenic wild-type rice seed extract, and Cry j 1 and Cry j 2 were mixed with the blood with reagents. The percentage of activated basophils was assessed by CD203c expression, a basophil activation marker. Results The percentage of activated basophils after the stimulation with Tg-rice seed extract was 4.5 ± 1.6% (mean ± SD) compared with 62.9 ± 20.2% after Cry j 1- and Cry j 2-stimulation (difference 58.4%, P < 0.001, 95% confidence interval 51.0–65.9%). Conclusions The results will contribute to the safety of Tg-rice seeds in terms of allergies.