(A) Schematic depiction of TBI, and IFN-γ and ruxolitinib administration in mice. After TBI, mice received syngeneic bone marrow transplantation (BMT) to rescue from bone marrow death on day 0. Survival (B), body weight as a percentage of initial weight (C), and clinical severity scores (D) from 2 independent experiments were combined, and data are shown as mean values ± SEM (IFN-γ alone group, n = 6; TBI alone group, n = 6; TBI + IFN-γ group, n = 10; TBI + IFN-γ + ruxolitinib group, n= 10). (E–M) Histology of mouse ileal sections 48 hours after TBI. H&E staining of ileum sections from mice receiving TBI (E), TBI + IFN-γ (F), or TBI + IFN-γ + ruxolitinib (G). (H–M) Confocal imaging of Lgr5-EGFP-ires-creERT2 mouse ileum sections. Immunofluorescence staining of cryptdin-1 (red, H-M), Lgr5-GFP+ (green, white arrows, H-J), Olfm4 (green) and DAPI (blue) (K-M) for mice that received TBI (H and K), TBI + IFN-γ (I and L), or TBI + IFN-γ + ruxolitinib (J and M). The results are representative of 2 separate experiments and illustrate the reduction in crypt numbers and the loss and absence of Paneth cells and rapidly cycling ISCs in ileum of TBI + IFN-γ–treated mice (F, I, and L). Scale bars: 100 μm.