ATG16L1 prevents intestinal GVHD by inhibiting epithelial necroptosis. (A-D) Mice receiving BM and T cells from donor LP/J mice as in Figure 1 were euthanized on day 28 after allo-HCT and analyzed for signs of intestinal GVHD (n = 11 [Atg16L1^f/f; f/f], n = 12 [Atg16L1^ΔIEC; ΔIEC], n = 8 [f/f Ripk3^−/−], and n = 8 [ΔIEC Ripk3^−/−]). (A) Colon length. (B) Pathology score of small intestine, colon, liver, and skin. Representative images (C) and quantification (D) of hematoxylin and eosin (H&E), TUNEL, and cleaved caspase 3 staining. Arrowheads indicate Paneth cells or IECs positive for the indicated markers. Scale bars, 10 µm. At least 50 crypts were quantified per mouse. Data points in A, B, and D represent individual mice. Bars represent mean ± standard error of the mean, and ≥2 independent experiments were performed. *P < .05, **P < .01, ***P < .001, ****P < .0001. SI, small intestine.