Figure 5Experimental design for blocking JNK/c-Jun signaling in the IMQ-induced skin inflammation model. c-Jun fl/fl, c-JunΔ/ΔCD11c-Cre, Tlr7-/- and Tlr7-/- c-JunΔ/ΔCD11c-Cre mice were treated with IMQ and JNK inhibitor SP600125 (JNKi, 15 mg/kg, i.p.) or vehicle for 5 consecutive days. Data information: Data are shown as mean ± SEM. P‐values were calculated by one-way ANOVA with Tukey Statistical significance: ns > 0.05, *P < 0.05, **P < 0.01, ***P < 0.001, **** P < 0.0001. See Appendix Table S3 for exact P‐values. B-E. After 5 days of treatment TEWL was measured on the back skin (B), epidermal thickness was analyzed on H&E stained sections (C), epidermal Ki-67+ cells (D) and the ratio of Ratio of K5 to K10 positive areas (E) were analyzed by immunofluorescence as described in Fig EV3 (B,C). (n = 4-15; 5 independent experiments). Data information: Data are shown as mean ± SEM. P‐values were calculated by one-way ANOVA with Tukey Statistical significance: ns > 0.05, *P < 0.05, **P < 0.01, ***P < 0.001, **** P < 0.0001. See Appendix Table S3 for exact P‐values. F-H. Quantification of immune cell populations as defined in Fig EV3 (E, F). Results are given as percentage of live, single cells. (n = 4-12; 3-4 independent experiments). Data information: Data are shown as mean ± SEM. P‐values were calculated by one-way ANOVA with Tukey Statistical significance: ns > 0.05, *P < 0.05, **P < 0.01, ***P < 0.001, **** P < 0.0001. See Appendix Table S3 for exact P‐values. Experimental design for blocking JNK/c-Jun signaling in c-Jun/JunB Δ/Δ K5-Cre-ERT2 mice. Psoriasis-like disease was induced by injection of Tamoxifen (i.p., 5 days). Treatment with JNK Inhibitor (15 mg/kg, every other day, i.p.) started on day 14 for 2 weeks. Representative images of ear, tail and paw of c-Jun/JunB Δ/Δ K5-Cre-ERT2 at the start (Day14) and end (Day 28) of treatment with JNK Inhibitor or vehicle. H&E stained sections of mouse ear from indicated mice. Bright-field images, Scale bar: 250 µm, Magnification: 10x. Psoriasis-like phenotype was scored from 0-4 for ear, tail, paw and snout. Shown is the cumulative score at therapy start (Day 14) and end (Day 28). Non-responders are c-Jun/JunB Δ/Δ K5-Cre-ERT2 mice treated with JNK Inhibitor, which showed disease-progression. (n = 2-8, 2 independent experiments). Data information: Data are shown as mean ± SEM. P‐values were calculated by paired, two-tailed t-test (L) Statistical significance: ns > 0.05, *P < 0.05, **P < 0.01, ***P < 0.001, **** P < 0.0001. See Appendix Table S3 for exact P‐values. Representative t-SNE- plots (n = 2-3) show the cutaneous immune cell phenotype at therapy end (Day 28). Numbers adjacent to gates give cell populations frequency among live, single, CD45+ cells. t-SNE Legend-Plot labels the populations defined by t-SNE- algorithm. Dermal γδ T cells (γδ TCRint+), Monocytes (CD11b+Ly6Chi), and Neutrophils (CD11b+Ly6G+) were analyzed by flow cytometry in mouse ear at the end of treatment (Day 28). Graphs show immune cells as % of live, single cells. (n = 2-8, 2 independent experiments). Data information: Data are shown as mean ± SEM. P‐values were calculated by Bonferroni multiple comparison test (N). Statistical significance: ns > 0.05, *P < 0.05, **P < 0.01, ***P < 0.001, **** P < 0.0001. See Appendix Table S3 for exact P‐values.