Treatment with JQ5, but not JQ1, can treat sclerodermatous cGVHD. (A-C) BALB/c mice were given TBI (700 cGy on day −1) followed by infusion of 10⁷ B10.D2 BM ± 1.8 × 10⁶ CD4 and 0.9 × 10⁶ CD8 T cells (day 0). JQ5- and JQ1-treated mice received treatment as in Figure 1 from days 20 to 45 posttransplant, n = 25/group. (A-B) From left to right, graphs show impact of JQ5 treatment on recipient survival, mean weights, clinical scores, and skin scores. Arrows on clinical and skin score plots indicate time of treatment initiation. (A) Although JQ5 did not significantly improve either weights or survival proportion, treated mice showed significantly reduced clinical scores, and skin scores as early as 10 days after initial treatment. (B) JQ1 treatment shows evidence of toxicity within 7 days of beginning therapy with no mice surviving beyond 2 weeks after treatment initiation. (C) Representative images of sclerodermatous mice with or without treatment with each drug. Images taken 45 days posttransplant, except for JQ1-treated mouse, where image was taken 34 days posttransplant. (D) Flow cytometry analysis of cytokine production from transplanted mouse lymph nodes shows a significant reduction in inflammatory cytokine production with JQ5 treatment, indicative of reduced disease, n = 5 per group. (E) Representative images of cryopreserved skin cross sections from mice 45 days posttransplant. Sections were stained with Masson trichrome. Images are ×200 magnification. (F) Quantification of trichrome⁺ area of skin cross sections in panel C shows a significant reduction in trichrome-positive area with JQ5 treatment, n = 4 per group. This correlates to a reduction in skin collagen deposition with treatment. *P < .05, **P < .01, ***P < .001, ****P < .0001.