Fig. 6: Increased TGF-β1 expression by psoriatic keratinocytes induced by IL-26.

a Expression fold change of TGFB1 in healthy skin (n = 40) and nonlesional (n = 199) and lesional (n = 120) skin from psoriasis patients using the SSF Bioinformatics hub. Data are represented as a box plot which bounds extends from the 25th to 75th percentiles, a middle line is plotted at the median, and whiskers go from the minimal to maximal value Data were statistically analyzed using one-way ANOVA followed by Tukey’s multiple comparisons test. ****p < 0.0001. b UMAP projection of the single-cell transcriptomes of total cells from nonlesional (top) and lesional (bottom) skin of 3 psoriasis patients colored according to the expression level of TGFB1. LC Langherans cells, KC keratinocytes, Mac/DC macrophages and dendritic cells, Fb fibroblasts, VE vascular endothelial cells. c Confocal microscopy image of lesional psoriatic skin representative of 5 patients stained for TGF-β mRNA. Dashed line delineates the dermo-epidermal junction. d Violin plots of TGFB1 expression by basal (KRT5+, KRT14+), proliferating (CDK1+, PCNA+), and differentiated suprabrasal (KRT1+, KRT10+) keratinocytes using single-cell RNAseq data from nonlesional and lesional skin of atopic dermatitis and psoriasis patients. e, Expression of TGFB1 in NHEK cells treated with different cytokines for 16 h. Data represent mean ± SEM of 3 biological replicates from one representative donor. Data were statistically analyzed using one-way ANOVA followed by Tukey’s multiple comparisons test. *p = 0.036; **p = 0.0063, ****p < 0.0001. f Expression of TGFB1 in healthy skin treated with IL-26 for 4 h. Data represent 3 independent donors. Data were statistically analyzed using two-tailed paired Student’s t-test. *p = 0.0122. g Expression of TGFB1 in NHEK cells treated overnight with IL-26 in the presence of blocking antibodies against IL-26, IL10R2, and IL20R1. Data represent mean ± SEM of 4 biological replicates from one donor. Data were statistically analyzed using one-way ANOVA followed by Tukey’s multiple comparisons test. ****p < 0.0001. h Expression of TGFB1 in WT or IL20R1^−/− HaCaT cells treated overnight with IL-26. Data represent mean ± SEM of 7 biological replicates. Data were statistically analyzed using one-way ANOVA followed by Tukey’s multiple comparisons test. ****p < 0.0001. i, Amounts of TGF-β1 produced by HaCaT cells treated overnight with T_H17 cell supernatants (from 5 independent donors) in the presence of blocking antibodies against IL10R2 and IL20R1, or control isotype. Data represent mean ± SEM. Data were statistically analyzed using one-way ANOVA followed by Tukey’s multiple comparisons test. *p = 0.0124 (aIL10R2), *p = 0.018 (aIL20R1). j Amounts of IL-26 (left) and IL-17A (right) produced by blood T_H17 cells (from 4 independent donors) treated for 7 days with IL-26-treated HaCaT cell supernatants in the presence of blocking antibodies against TGF-β. Data represent mean ± SEM. Data were statistically analyzed using two-tailed unpaired Student’s t-test. *p = 0.014. e–h Expression values measured by RT-qPCR were normalized to the reference gene GAPDH. Source data are provided as a Source Data file.