Fig. 6. Th2 cytokines upregulate IL-31RA to induce AHR with no effect on inflammation and goblet cell hyperplasia.

a, b Quantification of IL-31RA transcripts in mouse ASMC treated with increasing doses of IL-4 (n = 3) and IL-13 (n = 4) for 16 h. Two-way ANOVA test was used. Data shown as mean $\pm$SEM. c Wildtype (n = 4) and IL-31RA^–/– (n = 4) mice were treated intratracheally with IL-13 on days 0 and 6, and resistance in the lungs was measured with increasing doses of methacholine (MCh) using FexiVent. Data are shown as mean $\pm$SEM. Two-way ANOVA test was used. d ASMC isolated from wildtype (n = 3) and IL-31RA^–/– (n = 3) mice were seeded into collagen gels and treated with IL-13 to measure the contraction of collagen gels after 48 h. Unpaired t test was used. Data shown as mean $\pm$SEM. e Representative images of hematoxylin and eosin -stained lung sections from wildtype (n = 4) and IL-31RA^–/– (n = 4) mice treated with IL-13. Images were captured at ×20 magnification. Scale bar, 100 µm. f, g, h Quantification of inflammatory chemokines (CCL11, CCL24 and IL-17), Th2 cytokines (IL-4 and IL-5), and Th2 response-associated genes (ARG1, CHl3L3, and FIZZ1) in the whole lungs of wildtype (n = 4) and IL-31RA^–/– (n = 4) mice treated with IL-13. Data are shown as mean $\pm$SEM. Unpaired t test was used, and no statistical significance observed between groups. i Representative images of Alcian blue periodic acid-Schiff-stained lung sections from wildtype (n = 4) and IL-31RA^–/– (n = 4) mice treated with IL-13. Images were captured at ×20 magnification. Scale bar, 100 µm. j Quantification of goblet cell hyperplasia associated genes including GOB5 and MUC5AC transcript levels in the total lungs of wildtype (n = 4) and IL-31RA^–/– (n = 4) mice treated with IL-13. Data are shown as means $\pm$SEM. Unpaired t test was used, and no statistical significance observed between groups. At least two independent experiments produced similar results. Source data are provided as a Source Data file.