Fig. 6. Interleukin-1β mediated signaling between innate immune cells and OTULIN-deficient keratinocytes regulates skin inflammation.
a Schematic representation of NicheNet analysis identifying ligands secreted by innate immune cells that bind to receptors on keratinocytes, mediating changes in gene expression. Lesional skin is compared to non-lesional ΔKerOTULIN skin. b Heatmap of IL-1β, IL-1α, and IL-18 mRNA expression levels in single cells of control (WT, n = 1), and ΔKerOTULIN non-lesional (NL, n = 2) and lesional (L, n = 3) skin, as determined by scRNAseq. c Heatmap of average mRNA expression levels of genes involved in inflammasome signaling in control, non-lesional ΔKerOTULIN and lesional ΔKerOTULIN keratinocytes, as determined by scRNAseq analysis. d Representative pictures of back skin of mice treated with daily injections of 300 mg/kg Anakinra and untreated controls. Age of the mice is indicated and duration of treatment. H&E-stained skin showing the morphology of the lesion at the time of sacrifice. Scale bar: 200 μm. e Trans-epidermal water loss (TEWL) measurements of non-lesional (NL) and healed lesional (L) skin of mice treated with Anakinra compared to untreated lesional skin (treated NL, n = 5; healed L and untreated L n = 4; ***p < 0.001; ****p < 0.0001, One-way ANOVA with multiple comparisons). Data represent means ± SEM. f Representative pictures of back skin of mice treated with intraperitoneal injections of 40 mg/kg α-MCP-1 antibody twice weekly. Duration of treatment is indicated. H&E-stained skin showing the morphology of the lesion at the time of sacrifice. Scale bar: 200 μm. g TEWL measurements of non-lesional (NL) and healed lesional (L) skin of mice treated with α-MCP-1 antibody compared to untreated lesional skin (treated NL, n = 5; healed L and untreated L n = 4; ***p < 0.001; ****p < 0.0001, One-way ANOVA with multiple comparisons). Data represent means ± SEM.