Fig. 4: Chronic Daxx loss leads to increased inflammatory cytokines and pyoderma gangrenosum, an autoinflammatory neutrophilic disease.
a, Concentrations of cytokines in plasma (n = 6 mice per genotype). b, Incidence of skin lesions in the mice in the total group and stratified by sex. Data are the mean. c, DaxxF/F;Mx1Cre+/− mouse with skin lesions. d, Representative image of the spleens of control and Daxx-KO mice with skin lesions (left), and the spleen weight of mice with skin lesions (right; n = 6 mice per genotype). e, Skin lesion of a DaxxF/F;Mx1Cre+/− mouse (top; n = 3 biological replicates) compared with a human skin biopsy of a patient with pyoderma gangrenosum (bottom). Representative images of H&E-stained sections; the arrows indicate the site of the ulcer and fibrin layer. f, Immunofluorescence staining of Gr-1+ cells in sections of skin lesions (n = 2 independent experiments). Scale bars, 100 µm. g, Immunofluorescence staining of sections of skin lesions with citH3 (n = 2 independent experiments). The higher-magnification image (bottom) shows NETosis in a DaxxF/F;Mx1Cre+/− skin lesion. Scale bars, 100 µm and 20 µm (higher-magnification image). h, Number of B cells and neutrophils in the BM (top) and spleen (bottom) at 3 and 24 w.p.i. (n = 2 mice per genotype, except for WT at 3 w.p.i., where n = 4 mice). a,h, Boxplots show the minimum and maximum values (box boundaries) and the mean (horizontal line). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 and NS, not significant; non-parametric Wilcoxon rank test. Daxx F/F, Daxx KO and Daxx +/+, Daxx WT. Exact P values and numerical source data are provided.
