Figure 5.
Pharmacologic inhibition of IRE-1α/XBP-1 prevents cGVHD in MHC-mismatched BMT model. B6 to BALB/c BMT was carried out as in Figure 3. The recipients were left without treatment (n = 4) or IP injected daily with DMSO vehicle or with B-I09 at a dose of 25 mg/kg starting on day 0 and continued for 3 weeks (n = 8 per group). BMT recipients (n = 19) were monitored for cGVHD clinical scores and skin scores (A) and killed on day 30 (n = 4 per group) or 50 (n = 4 per group) after transplant, and spleens were subjected to flow cytometric analysis for surface expression of syndecan-1 and intracellular IgG1. Representative flow plots from day 50 for each group are depicted in panel B. Data from each group are quantified in panel C. Overall cGVHD clinical scores for the entire experimental time course were analyzed using a paired Student t test. For skin cGVHD clinical scores, a 2-tailed Student t test was performed for the final time point. P < .05 indicates statistical significance. Data were collected from n = 19 mice from 1 representative experiment. Veh, vehicle.