AMP derived from Xbp1-mediated 1C metabolism restrains the progression of DSS-induced colitis in an ILC-dependent manner. (A–F) Rag2 −/− mice were gavaged with H2O or AMP (800 mg/kg) at day 0 to day 5 during 3% DSS administered for 6 days. Experimental design (A). DAI scores (B) were monitored at the indicated time points. Representative large intestine images (C). Lengths of colons (D). Representative H&E histology sections of the colon. Scale bar, 500 μm (E). Histology scores (F). Data were compiled from two independent experiments and are shown as the mean ± SD (n = 6 per group). (G–L)Rag2−/−Il2rg−/− mice were gavaged with H2O or AMP (800 mg/kg) at day 0 to day 5 during 3% DSS treated for 6 days. Experimental design (G). DAI scores (H) were monitored every day during the experiments. Representative large intestine images (I). Lengths of colons (J). Representative H&E histology sections of the colon. Scale bar, 500 μm (K). Histology scores (L). Data were compiled from three independent experiments and are shown as the mean ± SD (n = 6 per group). (M–R) Sorted large intestinal ILC2s (Lin−CD127+KLRG1+) from WT (Xbp1+/+Il5RFP-Cre) or cKO (Xbp1f/fIl5RFP-Cre) mice were transferred into Rag2−/−Il2rg−/− mice during DSS-induced colitis. PBS was used as a vehicle control. Experimental design (M). DAI scores (N) were monitored at the indicated time points. The orange asterisk represents the comparison between the WT-ILC2 and PBS groups, and the green asterisk represents the comparison between the cKO-ILC2 and WT-ILC2 groups. Representative large intestine images (O). Lengths of colons (P). Representative H&E staining of the colon. Scale bar, 500 μm (Q). Histological severity scores of colons (R). Data were compiled from two independent experiments. Data are shown as the mean ± SD (n = 6 per group). *P < 0.05, **P < 0.01, ***P < 0.001.