Fig. 2: Minimal rescue of APLAID due to deletion of IL-6, caspase-1 or TNF.
a, A clinical APLAID skin score demonstrates persistent but attenuated skin inflammation of different Plcg2S707Y/+ knockout mice after weaning (Plcg2+/+, n = 19; Plcg2S707Y/+, n = 4; Plcg2S707Y/+IL-6−/−, n = 26; Plcg2S707Y/+caspase-1−/−, n = 17; Plcg2S707Y/+TNF−/−, n = 20; at 2–3 weeks of age). b, A growth curve exhibiting stunted weight gain during weekly assessments among Plcg2S707Y/+ knockouts (Plcg2+/+, n = 4; Plcg2S707Y/+, n = 5; Plcg2S707Y/+IL-6−/−, n = 5; Plcg2S707Y/+caspase-1−/−, n = 3; Plcg2S707Y/+TNF−/−, n = 4; at 2–4 weeks of age). c, Kaplan–Meier survival curve showing Plcg2S707Y/+ knockout mice with an impaired survival rate in comparison to Plcg2+/+ littermate controls after weaning (Plcg2+/+, n = 10; Plcg2S707Y/+, n = 15; Plcg2S707Y/+IL-6−/−, n = 8; Plcg2S707Y/+caspase-1−/−, n = 10; Plcg2S707Y/+TNF−/−, n = 12; at 3–7 weeks of age). d, Immune cell infiltrates were present in paws, ears, tails, lung, gut and spleen across all different mouse strains. One representative IHC section (from three independent experiments per genotype; at 4 weeks of age) of CD45+, MPO+ and F4/80+ stains is shown. e, ADVIA analyzer data of the blood show variable neutrophil counts and a mild decrease of lymphocytes (Plcg2+/+, n = 15; Plcg2S707Y/+, n = 3; Plcg2S707Y/+IL-6−/−, n = 8; Plcg2S707Y/+caspase-1−/−, n = 7; Plcg2S707Y/+TNF−/−, n = 5; at 4–5 weeks of age). f, Quantification of immunoglobulin subtypes measured by ELISA reveals abnormal levels similar to Plcg2S707Y/+ mice (Plcg2+/+, n = 9; Plcg2S707Y/+, n = 5; Plcg2S707Y/+IL-6−/−, n = 5; Plcg2S707Y/+caspase-1−/−, n = 5; Plcg2S707Y/+TNF−/−, n = 5; at 4 weeks of age). g, Cytokine assessment by a multiplex assay in the plasma of Plcg2 mice and different knockout mice demonstrates a large increase in G-CSF followed by IL-12p40 and eotaxin (n = 11 mice per genotype; at 4–6 weeks of age). Heat map colors represent mean cytokine values. Error bars represent the mean ± s.e.m. Statistical significance for skin score was determined by a two-way ANOVA for repeated measurements with Bonferroni post-test correction. Statistical significance for longitudinal weight data between two groups was determined by a two-sided paired t-test. The survival curves were analyzed by a Mantel–Cox test. Cytokine levels were established by an ordinary two-way ANOVA, and Bonferroni post-test correction was used to adjust for multiple testing.
