IFN-λ signaling in recipient tissue determines GVHD severity. (A) Survival by Kaplan-Meier estimates for B6.WT (n = 31) and B6.Ifnlr1^–/– (Ifnlr1^–/–, n = 31) recipient mice lethally irradiated (1000 cGy) and transplanted with BALB/c-derived BM and T cells. A non-GVHD control group received T cell–depleted BM only (TCD; n = 10). Data combined from 5 experiments. (B) Clinical GVHD scores + SEM. (C) Representative images of colon and SI at day 7 after BMT. (D) Semiquantitative GVHD histopathology scores at day 7 after BMT (WT and Ifnlr1^–/–, n = 9; TCD, n = 6, combined from 2 experiments). (E) Serum fluorescein isothiocyanate (FITC) dextran at day 7 post-BMT (WT, n = 10; Ifnlr1^–/–, n = 9; combined from 2 experiments). (F) Serum IFN-γ, IL-6, tumor necrosis factor (TNF), and IL-17A at day 4 post-BMT (WT and Ifnlr1^–/–, n = 23; TCD, n = 10; combined from 3 experiments). (G) IL-28A/B measured in sera, SI, and colon from naive and 24 hours postirradiation (1000 cGy) WT mice (n = 9, combined from 2 experiments). SI and colon mucosal homogenates were prepared, and the IL28-A/B amounts in mucosal supernatants corrected for each gram of tissue. (H) IL-28A/B concentration in serum and SI mucosal homogenates as for panel G at days 1, 3, and 7 after lethal irradiation (1000 cGy) and transplantation with BALB/c BM and T cells or TCD only (n = 9, combined from 2 experiments). (I-J) B6D2F1 recipients were transplanted with BM and T cells from WT or Ifnlr1^–/– donors. Survival (I) and GVHD clinical scores (J) (GVHD groups, n = 12; TCD, n = 8; combined from 2 experiments). Data are presented as mean ± SEM. P values were calculated by using the 2-tailed Mann-Whitney t test. Kaplan-Meier survival was compared by using the log-rank Mantel-Cox test. *P < .05, **P < .01, ***P < .001, ****P < .0001.