ATG16L1 in the intestinal epithelium protects against lethal GVHD mediated by RIPK1 and RIPK3. (A) Survival of Atg16L1^f/f and Atg16L1^ΔIEC mice receiving a chemotherapy conditioning regimen and transplanted with 5 × 10⁶ T-cell–depleted BM cells, with or without 4 × 10⁶ splenic T cells from donor LP/J mice. (B) Disease scores (see “Methods”) evaluated every 7 days after allo-HCT in (A). (C) Survival of chemotherapy-pretreated f/f Ripk3^−/− and Atg16L1^ΔIEC × Ripk3^−/− (ΔIEC Ripk3^−/−) mice transplanted with 5 × 10⁶ T-cell–depleted BM cells, with or without 4 × 10⁶ splenic T cells from donor LP/J mice. (D) Disease scores evaluated every 7 days after allo-HCT in (C). (E) Survival of chemotherapy-pretreated Atg16L1^f/f (f/f) and Atg16L1^ΔIEC (ΔIEC) mice that received GSK547 or control chow and were transplanted with 5 × 10⁶ T-cell–depleted BM cells and 4 × 10⁶ splenic T cells from donor LP/J mice. GSK547 was started 10 days before allo-HCT and continued until the end of the study. (F) Disease scores evaluated every 7 days after allo-HCT in (E). Data points in A, C, and E represent individual mice and are the combined results of 2 experiments performed independently. Data points in B, D, and F are mean disease scores of viable mice. Bars represent means ± standard error of the mean. For disease score, the area under the curve was determined for each mouse. *P < .05, ****P < .0001 analysis of variance with Tukey’s multiple-comparison test. HCT, hematopoietic cell transplantation; ns, not significant.