Figure 2.
IEC RIPK3 promotes MLKL-independent alloreactive T-cell responses. (A) Survival of the lethally irradiated WT and Mlkl−/− B6 recipients (BALB/c→B6) received BALB/c TCD BM alone (BM) or TCD BM plus CD4+ T cells (BM+CD4+ T). (B) Survival of the lethally irradiated WT and Mlkl−/− BALB/c recipients (B6→BALB/c) received B6 TCD BM alone (BM) or TCD BM plus CD4+ T cells (BM+CD4+ T). (C) KEGG pathway enrichment analyses of the DEGs in small intestine samples from WT and Ripk3−/− mice collected on day 17 after allo-HCT (P < .05, the P value is calculated by hypergeometric distribution). (D) Volcano plot showing fold changes of genes in small intestine samples collected from WT vs Ripk3−/− mice on day 17 after allo-HCT (left), or fold changes of genes in colonic biopsy specimens from patients with GVHD vs control colonic biopsy specimens from children without signs of intestinal injury (right). Significantly upregulated (red) and downregulated (blue) mouse or human homologous genes are shown. (E) Gene expression of chemokines and cytokines in the small intestine collected from WT, Ripk3−/−, and Vil-cre Ripk3fl/fl mice on day 17 after allo-HCT. (F) Gene expression of human chemokines in control colonic biopsy specimens and colonic biopsy specimens from patients with GVHD. (G) ELISA analysis of CXCL9 and CXCL10 proteins in the small intestine from the indicated B6 recipients (BALB/c→B6) 17 days after allo-HCT. (H) ELISA analysis of CXCL9 proteins in the small intestine from the indicated B6 recipients (BALB/c→B6) 7 days after allo-HCT. (I) Quantification of infiltrated CD3+ T cells in the small intestine from the indicated B6 recipients (BALB/c→B6) on day 7 after allo-HCT. Data shown are representative of 2 or 3 independent experiments. Data are shown as the mean ± SD (I), histology scores and chemokine concentrations are shown as the mean ± SEM (G-H). ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. Survival comparisons were evaluated by log-rank test (A-B). Multiple comparisons were evaluated by one-way ANOVA (G-I). ANOVA, analysis of variance; DEGs, differentially expressed genes; ELISA, enzyme-linked immunosorbent assay analysis; n.s., not significant; SD, standard deviation; SEM, standard error of the mean.

IEC RIPK3 promotes MLKL-independent alloreactive T-cell responses. (A) Survival of the lethally irradiated WT and Mlkl−/− B6 recipients (BALB/c→B6) received BALB/c TCD BM alone (BM) or TCD BM plus CD4+ T cells (BM+CD4+ T). (B) Survival of the lethally irradiated WT and Mlkl−/− BALB/c recipients (B6→BALB/c) received B6 TCD BM alone (BM) or TCD BM plus CD4+ T cells (BM+CD4+ T). (C) KEGG pathway enrichment analyses of the DEGs in small intestine samples from WT and Ripk3−/− mice collected on day 17 after allo-HCT (P < .05, the P value is calculated by hypergeometric distribution). (D) Volcano plot showing fold changes of genes in small intestine samples collected from WT vs Ripk3−/− mice on day 17 after allo-HCT (left), or fold changes of genes in colonic biopsy specimens from patients with GVHD vs control colonic biopsy specimens from children without signs of intestinal injury (right). Significantly upregulated (red) and downregulated (blue) mouse or human homologous genes are shown. (E) Gene expression of chemokines and cytokines in the small intestine collected from WT, Ripk3−/−, and Vil-cre Ripk3fl/fl mice on day 17 after allo-HCT. (F) Gene expression of human chemokines in control colonic biopsy specimens and colonic biopsy specimens from patients with GVHD. (G) ELISA analysis of CXCL9 and CXCL10 proteins in the small intestine from the indicated B6 recipients (BALB/c→B6) 17 days after allo-HCT. (H) ELISA analysis of CXCL9 proteins in the small intestine from the indicated B6 recipients (BALB/c→B6) 7 days after allo-HCT. (I) Quantification of infiltrated CD3+ T cells in the small intestine from the indicated B6 recipients (BALB/c→B6) on day 7 after allo-HCT. Data shown are representative of 2 or 3 independent experiments. Data are shown as the mean ± SD (I), histology scores and chemokine concentrations are shown as the mean ± SEM (G-H). ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. Survival comparisons were evaluated by log-rank test (A-B). Multiple comparisons were evaluated by one-way ANOVA (G-I). ANOVA, analysis of variance; DEGs, differentially expressed genes; ELISA, enzyme-linked immunosorbent assay analysis; n.s., not significant; SD, standard deviation; SEM, standard error of the mean.

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