Fig. 10: Deletion of IDO1 in lymphatic endothelial cells exacerbates psoriasis.

a Lymphatic collectors from Prox1-cre-ERT2-TdT-LoxP-IDO1 mice, visualized after tamoxifen treatment (+TMX), vs untreated (−TMX) (n = 24 biologically independent replicates). b Nodal LECs express tdTomato only after tamoxifen treatment (+TMX) (n = 24 biologically independent replicates). c Thoracic ducts and lymph nodes were harvested from tamoxifen-treated Prox1-Cre-ERT2-TdT-LoxP-Ido1 mice and tamoxifen-treated Prox1-Cre-ERT2-TdT controls (n = 24 biologically independent replicates). d LECs were sorted from the same mice as in (c) using CD31 and TdTomato as markers (n = 12 biologically independent replicates). e 3-HKA quantification in the lymphatic fluid and plasma (n = 4 biologically independent samples) of Prox1-Cre-ERT2-TdT-LoxP-Ido1 mice and Prox1-Cre-ERT2-TdT controls treated (+TMX) or untreated (−TMX) with tamoxifen. Data are presented as average ± SD of biological quadruplicates (n = 4) and analyzed by two-tailed paired student’s t test, p < 0.01 (**). f–i Psoriasis was induced in the Prox1-cre-ERT2-TdT-LoxP-Ido1 as described in Fig. 7, a more severe psoriasis as indicated by (f, g, i) histological evaluation and (h) animal survival curve, of tamoxifen-treated mice (+TMX) as compared to the untreated animals (−TMX) (n = 12 biologically independent samples). i Histological quantification is presented as number of keratin layers, quantified in biological replicates ± SD (n = 7 biologically independent samples). Data are presented as average ± SEM analyzed by two-tailed paired student’s t test. j Quantitative analysis of pro-inflammatory chemokines and cytokines present in skin lysates from Prox1-cre-ERT2-TdT-LoxP-Ido1 mice (+TMX) and (−TMX) tamoxifen, 4 days after psoriasis induction. Data from independent biological replicates (n = 4) plotted as mean relative expression ± SD. Significance levels are reported as p < 0.05 (*), p < 0.01 (**), and p < 0.001 (***) (two-way ANOVA followed by Tukey’s multiple comparison test). k Flow cytometry analysis of lymph node from the same mice as in (g, h); representative plot of ICOS⁺/Ki67⁺ CD8⁺ T cells. Bar graph report % of ICOS⁺/Ki67⁺ CD8⁺ T cells for each analyzed mouse and representative plot of CD44⁺/CD62L⁻ CD8⁺ T cells. 3-HKA (n = 4), imiquimod (n = 6), or 3-HKA plus imiquimod-treated C57BL/6J mice (n = 4). Data are presented as average ± SEM analyzed by two-tailed unpaired student’s t test, p < 0.001 (***). Source data for (a–c) and (j–k) are provided as Source data file.