Administration of Am80 ameliorates cGVHD. (A-D) Sublethally irradiated BALB/c recipients were transplanted from WT B10.D2 donors. The recipients received daily administration of ATRA (200 μg/mouse; A), Am80 (1.0 mg/kg of body weight; B), or vehicle solution orally after BMT and were assessed for clinical signs of cGVHD every 3 days. The skin cGVHD scores are shown. (C) Representative histopathology of skin and pathology score of skin, lung, liver, and colon in each group (n = 5-6 per group) on day 16 after BMT are shown. (D) PLN cells of the recipients on day 16 were stained for intracellular Foxp3. The percentages and absolute numbers of CD4⁺Foxp3⁺ Treg cells are shown. Data are from 1 representative of ≥ 2 independent experiments. (E) Sublethally irradiated BALB/c recipients were transplanted with 8 × 10⁶ TCD-BM cells plus 2 × 10⁶ total spleen T cells or CD25-depleted T cells from WT or IFN-γ^−/− B10.D2 donors. After BMT, recipients were given Am80 or vehicle solution. The skin cGVHD scores are shown. There were 6 recipients in each group; the data are from 1 representative of ≥ 2 independent experiments. (F-K) Sublethally irradiated BALB/c recipients were transplanted from WT (F), IL-17^−/− (G), and IFN-γ^−/− (H) donors. After BMT, recipients were given Am80 or vehicle solution. TGF-β mRNA expression in the ears on day 35 after BMT (F-H) and skin cGVHD scores (I-J) are shown. Data are from 1 representative of ≥ 2 independent experiments (n = 5 per group). (K) The skin cGVHD scores of BMT recipients treated with Am80 or vehicle solution orally daily after day 21 of BMT; data from 3 independent experiments were combined (n = 12-14 per group). *P < .05, **P < .01, and ***P < .005.