Figure 1. Endothelial-specific inhibition of the IFN-γ response ameliorates DSS-induced colitis in mice.

Mice with an endothelial cell–specific knockout of IFN-γ receptor 2 either from onset (Ifngr2^ΔEC, n = 11) or after tamoxifen induction (Ifngr2^iΔEC, n = 7) and mice with floxed Ifngr2 alleles (Control, both n = 9) were compared. Colitis was induced by addition of 2.5% DSS to the drinking water for either 1 cycle (acute colitis) or 3 cycles (chronic colitis, 4 Ifngr2^ΔEC and 5 Ifngr2^fl/fl). (A) Endothelial cell–specific knockout of the receptor was analyzed by immunofluorescent costaining of IFN-γ receptor 2 (red) and the endothelial cell marker CD31 (green). A strong expression of the receptor in colon epithelial cells was maintained in all animals (asterisks). The receptor was absent in endothelial cells of knockout animals (green, arrows) and present in colon vessels of control animals (yellow, arrowheads). Nuclei were stained with DRAQ5 (blue). Scale bars: 50 μm. (B–D) Colon inflammation was analyzed by endoscopic score (B), measurement of colon length (C), and histologic examination after H&E staining (D). Scale bars: 100 μm. Representative pictures are shown. All graphs represent data quantification with means ± SD. Two-tailed, unpaired Student’s t test (B and C) was used to determine statistical significance (*P < 0.05, ***P < 0.001, ****P < 0.0001).