IL-25 and IL-33 may somehow contribute to the development of HDM-induced AR.

<p>(A) Scheme of intranasal treatment of mice with HDM or PBS. (B) Detection of IL-25 in nose of wild-type and IL-25^−/− mice treated with HDM or PBS on Day 30 as in (A). The sections were stained with anti-mouse IL-25 Ab. IL-25 was detected in the cytoplasm of epithelial cells (brown) from HDM-treated wild-type mice, but not PBS-treated wild-type mice or PBS- and HDM-treated IL-25^−/− mice. Arrowheads indicate IL-25-positive epithelial cells (×400). (C) Detection of IL-33 in nose from wild-type and IL-33^−/− mice treated with HDM or PBS on Day 30, as in (A). The sections were stained with anti-mouse IL-33 Ab. IL-33 was detected in the nuclei of epithelial cells (red) from PBS-treated wild-type mice, but not HDM-treated wild-type mice or PBS- and HDM-treated IL-25^−/− mice. Arrowheads indicate IL-33-positive epithelial cells. Red shows IL-33 staining, and blue shows DAPI staining (×400). Data show a representative result from 3–7 mice in each group.</p

Histological analysis for infiltration of leukocytes and hyperplasia of goblet cells.

<p>Histological analysis of nasal mucosa (maxillary turbinate) from wild-type, IL-25^−/− and IL-33^−/− mice 48 hours after the last inhalation of HDM or PBS. (A) H&E staining. After inhalation of HDM, but not PBS, eosinophils were observed in the nasal mucosa of wild-type and IL-25^−/− mice but hardly detectable in mucosa from IL-33^−/− mice. Arrowheads indicate eosinophils. (B) PAS staining. After inhalation of HDM, but not PBS, goblet cell hyperplasia was similarly observed in the nasal mucosa of both wild-type and IL-25^−/− mice, but it was markedly reduced in IL-33^−/− mice compared with wild-type mice. Arrowheads indicate PAS-positive goblet cells. Data show a representative result from 3–7 mice in each group (bar  = 20 µm).</p

IL-33 produced by immune cells derived from bone marrow stem cells is not crucial for development of HDM-induced AR.

<p>(A) H&E staining of nasal mucosa, (B) the number of eosinophils in the nasal mucosa and (C) cytokine levels in the culture supernatants of HDM-stimulated LN cells from wild-type mice injected with wild-type bone marrow (BM) cells or IL-33^−/− BM cells, 48 hours after the last inhalation of HDM (n = 10) or PBS (n = 5). Histological data show a representative result from each group (bar  = 20 µm). Data show the mean + SEM. Med =  Medium alone.</p

IL-33, but not IL-25, is required for IL-5 production, but not Th2 cell differentiation, during HDM-induced AR in mice.

<p>(A, B) HDM-specific LN cell proliferative responses and cytokine production of wild-type and IL-25^−/− mice (A) and of wild-type and IL-33^−/− mice (B) 48 hours after the last inhalation of HDM or PBS. Data show the mean + SEM (PBS, n = 3–4; HDM, n = 6–7), and the results generated in one of two independent experiments, each of which gave similar results. * P<0.05. (C–F) The proportion of cytokine-producing CD3⁺ CD4⁺ T cells in cervical LN cells cultured with and without HDM <i>in vitro</i>, as in (A) and (B). (C, E) FACS data show the results for LN cells pooled from 5 mice in each group, and a representative result of 5 independent experiments. (D, F) Data show the mean + SEM of 5 independent experiments in (C) and (E). Med =  Medium alone.</p

Pathogen detection between asthma inpatients (exacerbation) and stable outpatients (%).

<p>*p < 0.05 by Pearson’s χ² test</p><p>†p < 0.05, by multiple logistic regression analysis.</p><p>Pathogen detection between asthma inpatients (exacerbation) and stable outpatients (%).</p

Pathogens detected.

<p>Pathogens detected.</p

Pathogen detection from asthma exacerbation patients after a common cold.

<p>Pathogen detection from asthma exacerbation patients after a common cold.</p

Patients’ characteristics by pathogen detection (n = 48).

<p>Post ACQ and FeNO levels were measured one month after asthma exacerbation.</p><p>*p < 0.05, Mann-Whitney U test</p><p>†p < 0.05, multiple logistic regression analysis.</p><p>Patients’ characteristics by pathogen detection (n = 48).</p