IL-22BP deficiency releases IL-22 signaling on the FAE. (A) PP tissues from WT and Il22ra2−/− mice were immunostained with anti–IL-22BP antibody. Green colors show IL-22BP–positive cells, and blue show nuclei. (B) Both Il22ra2+/− and Il22ra2−/− mice were intravenously administered with recombinant IL-22 protein. After 15 min, PP tissues were collected. Tissue sections prepared from these mice were immunostained with anti-pSTAT3 antibody. Green colors show pSTAT3, and blue show nuclei. Dotted lines indicate FAE. Bars, 40 µm. Data are pooled from at least three mice of each genotype. (C) Relative Il22ra1 mRNA expression of FAE and VE from both Il22ra2+/− and Il22ra2−/− mice. Circles and squares show VE and FAE, respectively. Solid symbols indicate expression profiles of Il22ra2+/− mice, and open ones indicate those of Il22ra2−/− mice. Data were normalized with Gapdh (n = 7). Data are representative of three independent experiments. (D) Relative Il22ra1 mRNA expression of intestinal organoids stimulated with RANKL and LT α1β2 for 24 h (n = 4). Data are representative of two independent experiments. Means ± SEM. are shown. One-way ANOVAs with Bonferroni’s (C) or Dunnett’s (D) post hoc test were used for statistical analyses. **, P < 0.01.