Fig. 6: Loss of A8 in epidermal cells improves skin and systemic disease in JunB^∆ep mice.

a Representative pictures of control, JunB^∆ep and JunB^∆epS100a8^∆ep mice, H&E staining of snout skin sections in indicated mice and IF of filaggrin, loricrin and Ki67 (red) co-stained with K5 or K14 (green), as indicated. Nuclei are stained with DAPI. Black scale bar, 100μm. White scale bars, 200μm. b Skin disease severity scoring from 0 (no lesions) to 4 (severe lesions in the face and ventral skin) of control, JunB^∆ep and JunB^∆epS100a8^∆ep mice. c Epidermal thickness (µm) measured on facial skin sections of mutant mice. Each dot represents the mean of 4 measurements for a single mouse. d SA CFUs in the skin of the indicated mice. e Protein levels of IL-17A, IL-6, IL-36β, MPO, NE, A8, A9 and CP in skin lysates from control (n = 5 < 6), JunB^∆ep (n = 5 < 7) and JunB^∆ep S100a8^∆ep (n = 8 < 9) mice normalized ([C]/[Cmax]) by row. The maximum absolute value ([Cmax]) in ng/ml is IL-17A: 2.72, IL-6: 1.79, IL-36β: 1.2, MPO: 22.04, NE: 2.36, A8: 5.63, A9: 4.46, CP: 9.63. f Percentage of CD45⁺ skin neutrophils (CD11b⁺, Ly6C^+, Ly6G⁺) in the indicated mice. g Flow cytometric analysis of splenic neutrophils (CD11b⁺, Ly6C⁺ and Ly6G⁺) in indicated mice, shown as percentage (%) of CD45⁺ cells in control, JunB^∆ep and JunB^∆ep S100a8^∆ep mice. h Blood granulocyte counts in control, JunB^∆ep and JunB^∆epS100a8^∆ep mice. i Protein levels of circulating MPO, NE, A8, A9, CP, IgE and IL-17A in the serum of control (n = 4 < 7), JunB^∆ep (n = 3 < 9) and JunB^∆ep S100a8^∆ep (n = 5 < 7) mice normalized ([C]/[Cmax]) by row. The maximum absolute value ^[)([Cmax]) in ng/ml is MPO: 30.68, NE: 6.35, A8: 0.53, A9: 0.73, CP: 37.95, IgE: 5499.17, IL-17A: 0.74. j Representative μCT images of the tibiae (left) and quantification of the cortical thickness of the tibiae (right). k Quantification of BV/TV and BMD of the tibiae in the indicated groups. Dot plots represent mean ± SEM. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001. Heat maps represent [C]/[Cmax] means, scaled by row, *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p ≤ 0.0001 compared to control mice and ^#p ≤ 0.05, ^##p ≤ 0.01, ^###p ≤ 0.001, ^####p ≤ 0.0001 compared to JunB^∆ep mice. One-way ANOVA with Fishers’ LSD test was used for statistical grouped analysis, and unpaired 2-tailed Student’s t-test with Welch’s correction was applied to compare statistical difference between 2 groups (gray stars).