LTβR signaling in epithelial cells inhibits intestinal epithelial injury by promoting IL-23- driven IL-22-dependent tissue protective responses. Ltbrfl/fl and Vil-Ltbr−/− mice (n=5) were treated for 5 days with 3.5% DSS. (a) Weight loss and (b) survival. (c) Colon length, and (d) hematoxylin and eosin staining and histological score of colon sections at day 11. (e) Intestinal epithelial cell proliferation was analyzed after BrdU pulse injection on day 8. Ten crypts from the colons of 5 mice per genotype were analyzed. (f–j) Expression of the indicated genes (f–i) and IL-23 production in culture supernatants of colons (j) was evaluated at day 5. (k) Ltbrfl/fl and Vil-Ltbr−/− mice (n=3–4) were treated for 5 days with 5% DSS. 10 µg of plasmid encoding empty vector (pRK) or IL-23-expressing plasmid (IL-23Fc) was injected intravenously at day 1. Colonic expression of Il22 mRNA was evaluated at day 5. For mRNA expression, data are normalized to Hprt. *P<0.05; **P<0.01; ***P<0.001 (Student’s t-test). Data are representative of two (e, j, k) or three (a–d, f–i) independent experiments. Error bars represent SEM.