Sublingual administration of Can f 1‐2‐4‐6 ameliorates AHR and TH2 but not TH17 cell responses to dog allergen extracts. (A) Mice were sublingually administered either PBS or Can f 1‐2‐4‐6 protein 3 times per week for four weeks followed by i.n. sensitization with either PBS or dog allergen extracts (1 μg) on day 28 and 5 i.n. challenges (10 μg total) on days 35–39, mice were sacrificed on day 43; PBS sublingual, PBS i.n. (open square, B–F n = 8), PBS sublingual, dog allergen extracts (red circle, B–F n = 10), Can f 1‐2‐4‐6 sublingual, dog allergen extracts (open purple triangle, B–F n = 11). (B) Total number of cells in the BAL. (C) Number of eosinophils in the BAL. (D) Number of T cells in the BAL. (E) Frequency of Foxp3+ cells among total CD4+ cells and mean fluorescence intensity (MFI) of Foxp3 expression on gated Treg cells from the BAL, lung and mLN. (F) Frequency of IL‐5+ IL‐13+,IL‐4+, IL‐17+ and IFN‐γ+ cells among total CD4+ cells from the BAL and lung tissue. (G–I) Airway resistance to increasing doses of methacholine as measured by FlexiVent (PBS sublingual, PBS i.n. n = 6, PBS sublingual, dog allergen extracts n = 10, Can f 1‐2‐4‐6 sublingual, dog allergen extracts n = 10). (G) Overall resistance Rrs. (H) Elastance Ers. (I) Newtonian resistance Rn. (J) Dog allergen‐specific serum IgG1 and total serum IgE ELISA representative of 3 experiments (PBS sublingual, PBS i.n. n = 3, PBS sublingual, dog allergen extracts = 5, Can f 1‐2‐4‐6 sublingual, dog allergen extracts n = 4). Can f 1‐specific IgG1 (various dilutions) and IgE (1:3 dilution) was also measured (PBS sublingual, PBS i.n. n = 5, PBS sublingual, dog allergen extracts = 6, Can f 1‐2‐4‐6 sublingual, dog allergen extracts n = 7). (K) Number of neutrophils in the BAL (PBS sublingual, PBS i.n. n = 5, PBS sublingual, dog allergen extracts n = 5, Can f 1‐2‐4‐6 sublingual, dog allergen extracts n = 5). N.D. Denotes not determined. One‐way ANOVA with Bonferroni's post‐test was performed to adjust for multiple comparisons. *p < .05, p < .01, ***p < .001, ****p < .0001