Figure 1.
JQ5 and JQ1 treat murine cGVHD/BO. Results are from BO cGVHD transplants. B10.BR mice were conditioned with 120 mg/kg Cytoxan (cyclophosphamide) (days −3, −2) and 7.6 Gy total body irradiation (TBI) (day −1). On day 0, recipients received 10 × 106 purified BM cells ± 73.5 × 103 B6 purified T cells from C57BL/6. Groups included a BM-only negative control, a WT BM and T-cell–positive control, and mice that were given each treatment either JQ5 (75 mg/kg 3×/wk) or JQ1 (50 mg/kg 3× per week) from day 28 to day 49 posttransplant. Results shown are pooled from 3 transplant replicates. Results of pulmonary function tests taken on day 49 posttransplant include measures of resistance, elastance, and compliance. Significant improvement in pulmonary function across multiple parameters was observed with both JQ5 (A; n = 22/BM-only, n = 17/cGVHD, n = 15/JQ5) and JQ1 (B; n = 18/BM-only, n = 20/cGVHD, n = 18/JQ1) treatment. Representative images of cryopreserved lung sections from mice 49 days posttransplant. (C-D) Sections were stained with Masson trichrome and analyzed for collagen deposition. Quantification of the trichrome positive area is in the furthest right panel. This deposition is significantly reduced in both the JQ5-treated mice (C; n = 8/BM-only, n = 11/cGVHD, n = 8/JQ5) and the JQ1 treated mice (D; n = 7/BM-only, n = 8/cGVHD, n = 8/JQ1). (E-F) Sections were stained with anti IgG FITC and DAPI and show a reduction of IgG+ tissue in both JQ5-treated mice (E; n = 5/BM-only, n = 5/cGVHD, n = 4/JQ5) and the JQ1-treated mice (F; n = 5/BM-only, n = 5/cGVHD, n = 4/JQ1). Quantification of FITC+ area is shown in panels furthest to the right. All images are at ×200 magnification. Statistics shown are results of an unpaired t test with Bonferroni corrected P values when appropriate. *P < .05, **P < .01, ***P < .001, ****P < .0001.

JQ5 and JQ1 treat murine cGVHD/BO. Results are from BO cGVHD transplants. B10.BR mice were conditioned with 120 mg/kg Cytoxan (cyclophosphamide) (days −3, −2) and 7.6 Gy total body irradiation (TBI) (day −1). On day 0, recipients received 10 × 106 purified BM cells ± 73.5 × 103 B6 purified T cells from C57BL/6. Groups included a BM-only negative control, a WT BM and T-cell–positive control, and mice that were given each treatment either JQ5 (75 mg/kg 3×/wk) or JQ1 (50 mg/kg 3× per week) from day 28 to day 49 posttransplant. Results shown are pooled from 3 transplant replicates. Results of pulmonary function tests taken on day 49 posttransplant include measures of resistance, elastance, and compliance. Significant improvement in pulmonary function across multiple parameters was observed with both JQ5 (A; n = 22/BM-only, n = 17/cGVHD, n = 15/JQ5) and JQ1 (B; n = 18/BM-only, n = 20/cGVHD, n = 18/JQ1) treatment. Representative images of cryopreserved lung sections from mice 49 days posttransplant. (C-D) Sections were stained with Masson trichrome and analyzed for collagen deposition. Quantification of the trichrome positive area is in the furthest right panel. This deposition is significantly reduced in both the JQ5-treated mice (C; n = 8/BM-only, n = 11/cGVHD, n = 8/JQ5) and the JQ1 treated mice (D; n = 7/BM-only, n = 8/cGVHD, n = 8/JQ1). (E-F) Sections were stained with anti IgG FITC and DAPI and show a reduction of IgG+ tissue in both JQ5-treated mice (E; n = 5/BM-only, n = 5/cGVHD, n = 4/JQ5) and the JQ1-treated mice (F; n = 5/BM-only, n = 5/cGVHD, n = 4/JQ1). Quantification of FITC+ area is shown in panels furthest to the right. All images are at ×200 magnification. Statistics shown are results of an unpaired t test with Bonferroni corrected P values when appropriate. *P < .05, **P < .01, ***P < .001, ****P < .0001.

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