Figure 3. Inhibition of MALT1 proteolytic activity attenuates CARD14E138A‐induced psoriasis.

• A
  Schematic representation of the experimental set‐up of CARD14^E138A induction and MALT1 inhibitor treatment.
• B
  Cleavage of MALT1 substrates CYLD and BCL10 as analyzed by Western blotting of lysates of ear tissue of mice 4 days after treatment with tamoxifen and MALT1 inhibitor or vehicle. Actin is shown as a loading control. Each lane represents one mouse.
• C
  Changes in relative ear thickness and body weight in vehicle‐ and MALT1 inhibitor‐treated mice upon CARD14^E138A induction. M1 inh = MALT1 inhibitor, WT = K14creER^Tg/+ Rosa26^+/+, ieCARD14^E138A = K14creER^Tg/+ Rosa26^{LSL‐CARD14‐E138A/+}. Combined results of two independent experiments are shown (WT + vehicle: n = 9, WT + M1 inh: n = 8, ieCARD14^E138A + vehicle: n = 9, ieCARD14^E138A + M1 inh: n = 10).
• D, E
  (D) Representative histological sections of ear tissue stained with hematoxylin and eosin and (E) measurements of epidermal thickness of tamoxifen‐treated mice. Combined results of two independent experiments are shown. Each symbol represents the mean of at least ten epidermal thickness measurements for each ear; the line represents the mean value.
• F
  IL‐6 and IL‐17a production by ear‐draining lymphocytes upon ex vivo restimulation with anti‐CD3/anti‐CD28 for 3 days (n ≥ 3 biological replicates).
• G
  Heatmap showing relative mRNA expression levels of the indicated genes in ear tissue normalized to reference genes. Values represent median of each group (n ≥ 3).

Data information: Statistics: Data are representative for two independent experiments. Error bars reflect SEM. P‐values were determined using REML analysis (C), two‐way ANOVA with Sidak correction for multiple comparisons (D), or a Mann–Whitney U‐test (E) (*P < 0.05, ***P < 0.001, ****P < 0.0001).Source data are available online for this figure.