Fig. 7. IFNβ activated Erk2 in lung TNFR2⁺ cDC2s to promote FAO.

(A and B) Flow cytometry analysis of eosinophils in the BALF of WT, Erk2^f/fCD11c^cre, and Stat3^f/fCD11c^cre mice treated with HDM or HDM/IFNβ (0.2 μg) (n = 4 mice per group). Data are representative of three independent experiments. (C) Flow cytometry analysis of pErk1/2 in HDM mice treated with IFNβ (0.2 μg) (n = 3 to 4 mice per group). Data are representative of three independent experiments. (D) Lung CD45.1⁺TNFR2⁺cDC2s from HDM-induced asthmatic mice were adoptively transferred into IFNAR1^−/− CD45.2 recipient mice. Recipient mice were treated with IFNβ (1 μg). Flow cytometry analysis (left) and frequency (right) of pErk1/2 in CD45.1⁺ TNFR2⁺cDC2s after IFNβ treatment (n = 3 mice per group). Data are representative of two independent experiments. (E to G) Flow cytometry analysis of CD36 (E), pAMPK (F), and CPT1a (G) expression in TNFR2⁺ cDC2s from Erk2^f/f and Erk2^f/fCD11c^cre mice at steady state (n = 3 mice per group). Data are representative of three independent experiments. (H) Experimental design for adoptive transfer. Lung TNFR2⁺ cDC2s cells were sorted out of asthmatic CD45.1 mice on day 16. Sorted TNFR2⁺ cDC2s cells were treated with PBS or GDC-0994 (50 nM) for 30 min at 37°C. About 60,000 treated TNFR2⁺ cDC2s cells were transferred intranasally into IFNAR1^−/− recipient mice. Recipient mice were treated with IFNβ (1 μg) or PBS. (I and J) Flow cytometry analysis of pAMPK (I) and CPT1a (J) expression in CD45.1⁺TNFR2⁺cDC2s after IFNβ or IFNβ plus Erk1/2 inhibitor (GDC-0994) treatment (n = 3 mice per group). Data are representative of two independent experiments. Graphs represent the mean, with error bars indicating SEM. P values were determined by one-way ANOVA with Tukey’s multiple comparison test (J) or by unpaired Student’s t test (A to G and I). Rabbit mAb isotype control staining for pAMPK and pErk1/2 can be found in fig. S6.