The colitis-protective effect in Shp2^M KO mice is abrogated in the absence of IL-10 function. (A–C) DKO and control mice were fed with 1.5% DSS. (A) Body weight loss, diarrhea, and rectal bleeding were monitored daily. (B) Colon length was measured at day 7. (C) The levels of inflammatory cytokines were measured in colon homogenates by ELISA. n = 5–6. (D–G) Mice were injected intraperitoneally with 20, 40, and 40 µg anti–IL-10 or IgG isotype at days 1, 3, and 5 after DSS challenge, respectively. (D) Body weight loss, diarrhea, and rectal bleeding were monitored daily. (E and F) Colon length and histological changes were measured at day 7. (G) The levels of TNF-α, IL-6, and MCP-1 in culture supernatant from colon tissues were measured by ELISA. n = 5–8. (H) CLPMs were treated with culture supernatant from coCM in the presence of anti–IL-10 or IgG isotype; the phosphorylation of STAT3 was evaluated by Western blot. Data are mean ± SEM and are representative of two independent experiments. *, &, and #, P < 0.05; **, P < 0.01; two-tailed unpaired Student’s t test. n.s., not significant.