Figure 8.

KLPJ-mediated colitis depends on caspase-1/11, but not NLRP3 or NLRC4. (A) Schematic of the experiment for the effects of caspase-1/11 KO (CKO), NLRP3 KO (N3KO), and NLRC4 KO (N4KO) on KLPJ-mediated colitis. (B) Colon length in caspase-1/11 KO (CKO+KLPJ), NLRP3 KO (N3KO+KLPJ), and NLRC4 KO (N4KO+KLPJ) or WT (WT+KLPJ) mice after infusing KLPJ (n = 6). WT+PBS, CKO+PBS, N3KO+PBS and N4KO+PBS, controls. (C) ELISA of tumor necrosis factor α (TNFα), IL6, and IL18 in the mixed samples of colon tissues of WT and caspase-1/11 KO mice (n = 6). (D) CFUs of KLPJ in colon contents of mice. Bacteria (10⁹) were orally infused and then CFU were counted after 7 days. (E) Schematic of the effects of KLPJ on the DSS-mediated colitis in CKO mice. (F) Survival rates of WT and their littermate caspase-1/11 KO mice (n = 12) after DSS. (G) Body weight changes of WT and their littermate caspase-1/11 KO mice (n = 12) after DSS. (H) DAI of WT and their littermate caspase-1/11 KO mice (n = 12) after DSS. (I) Colon length of WT and their littermate caspase-1/11 KO mice (n = 6) after DSS. (J) H&E staining of colon tissues of WT and their littermate caspase 1/11 KO mice (3 slides/mouse, n = 6) after DSS. Scale bars: 40 μm. (K) ELISA of TNFα, IL6, and IL18 in the mixed samples of colon tissues of WT and their littermate caspase-1/11 KO mice (n = 6) after DSS. (L) Flow cytometry of CD45⁺CD11b⁺Ly6G⁺, CD45⁺CD11b⁺CD103^-MHCII⁺Ly6C⁺, or CD45⁺CD4⁺IFNγ⁺ immune cells in the colon tissues of WT and their littermate caspase-1/11 KO mice (mixed sample per 2 mice, n = 6) after DSS. WT and CKO mice with (WT+KLPJ or CKO+KLPJ) or without (WT+PBS or CKO+ PBS) gavage of KLPJ. (F) Wilcoxon test; (G and H) 1-way analysis of variance test; (B–D, I, K, and L) Student t test; and (J) Mann–Whitney U test. ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001. Data are representative of at least 2 experiments.