IL-22 regulates epithelial functions through Stat3 phosphorylation. (A–E) Hh+AOM-treated mice were injected with isotype control, anti–IL-22, anti-IL6R, anti–IL-17, or anti-Thy1 (B and E) for 1 wk. (A) Colonic phospho-Stat3-Y705 expression (bars, 25 µm). Arrows indicate pStat3⁺ cells in the cLP. (B) Immunoblot for phospho-Stat3 and total Stat3 in colonic epithelial and lamina propria cells. (C and D) Blocking of IL-22 reduces epithelial proliferation. (C) Ki-67 expression in freshly isolated EC from Hh+AOM mice (n = 4) and anti–IL-22 treated mice (n = 4). Gated on live, Epcam⁺, CD45⁻ cells. (D) Cyclin D1 expression in dysplastic epithelial cells of Hh+AOM mice after 1 wk isotype or anti–IL-22 treatment (top). Cyclin D1 mRNA expression in isolated EC (bottom). (E) mRNA expression in EC. Data are shown as means and SEM of n = 2–5 per group. Results are representative of at least two independent experiments. *, P < 0.05; ***, P < 0.001; ****, P < 0.0001, one-way ANOVA with Bonferroni’s post test (E) or unpaired Student’s t test (C and D).