RIPK1 S161 phosphorylation sensitizes the cecum to TNF-induced damage and is important for TNF-induced lethality in mice. (A and B) Survival curves and body temperature of 8- to 12-wk-old male littermate mice of the indicated genotypes after TNF injection (400 μg/kg, i.v.). (C) Survival curves and body temperature of 8- to 12-wk-old male littermate Ripk1^S161E/S161E mice after i.v. injection with TNF of the indicated doses. (D) Representative photos and H&E staining images of ceca from three mice of each indicated genotype (50 μg/kg TNF treated for 6 h, i.v.). Scale bars, 100 μm. All mice were 8- to 12-wk-old male littermates. (E) 6- to 8-wk-old male littermate mice were treated with or without cecectomy and then injected with TNF after 4 wk (150 μg/kg i.v. for Ripk1^+/+ mice and 25 μg/kg i.v. for Ripk1^S161E/S161E mice). Survival curve is presented as a Kaplan–Meier plot, and the log-rank (Mantel–Cox) test (two-sided) is performed to determine statistical significance. ns, P ≥ 0.05; *P < 0.05; **P < 0.01; ***P < 0.001. Data of body temperature are presented as mean ± SD. The above experiments were independently performed twice. All mice used in this work were on a C57BL/6 background.