Figure 6.
TNFα and type I interferon signaling mediate anti-CD40-induced liver damage and cytokine release syndrome, respectively
(A) Heatmap showing differentially expressed genes in the KEGG TNF signaling pathway in livers from no ABX and ABX mice 24 h after treatment with anti-CD40 (100 μg i.p.). Intensity represents the Z score of log2 library size normalized counts.
(B–H) Levels of (B) ALT, (C) TNFα, (D) IL6 in serum, (E) number of monocytes/macrophages (CD11b+Ly6G–) per gram of liver, frequency of liver monocytes/macrophages expressing (F) CD80 or (G) CD86, and (H) number of neutrophils (CD11b+Ly6G+) per gram of liver 24 h after control (PBS) or anti-CD40 treatment. Indicated groups were also treated concurrently with PBS or anti-TNF (200 μg i.p.).
(I) Heatmap showing selected downregulated interferon stimulated genes in livers from no ABX and ABX mice 24 h after treatment with anti-CD40.
(J–L) Levels of (J) ALT, (K) TNFα, and (L) IL6 in serum in co-housed Ifnar−/− or wild-type C57BL/6 (Ifnar+/+) mice after control (PBS) or anti-CD40 treatment. n = 7–10 mice per group.
Statistical significance was determined using a Mann-Whitney test. ∗∗p ≤ 0.01; ∗∗∗p ≤ 0.001; ∗∗∗∗p ≤ 0.0001. N.S., not significant. Data are represented as mean ± SEM. Results shown are from single independent experiments.