JWH-133, but not THC, mitigates the severity of chronic GVHD. (A-C) Lethally irradiated Balb/c mice received transplants of CB2R^eGFP BM alone or together with spleen cells (adjusted to yield an αβ T-cell dose of 0.6 × 10⁶). Macrophages were isolated from the liver, lung, and spleen of mice 14 days posttransplantation. eGFP expression on macrophages from BM control and GVHD mice is shown in panel A. Naïve CB2R^eGFP mice not undergoing transplantation are shown for comparison. Results are from 4 to 5 mice per group. Representative histogram of CB2R-eGFP expression on splenic macrophages from mice in panel B. Normal B6 mice and naïve CB2R^eGFP mice not undergoing transplantation are shown for comparison. CB2R mRNA expression from flow-sorted CD11b⁺ F4/80⁺ macrophages obtained from the spleen on day 14 is depicted in panel C. Results for GVHD mice were pooled from 2 to 3 mice per data point. (D-F) Lethally irradiated Balb/c mice received transplants of B10.D2 BM alone or with 20 × 10⁶ spleen cells. Animals that received spleen cells were treated with JWH-133 (1.5 mg/kg), THC (20 mg/kg), or a vehicle control for 35 to 40 days beginning on day 0. Representative hematoxylin and eosin–stained sections of the skin on day 35 are shown in panel D, and cumulative pathological skin scores from replicate animals 35 to 40 days posttransplantation are depicted in panel E. Original magnification is ×100 for photomicrographs. (F) mRNA expression of TGF-β, GAL-3, and α-SMA in the skin of animals (n = 7-15 mice per group) 35 to 40 days posttransplantation. Results are from 6 experiments. Data in panels A, C, E, and F are presented as the mean ± standard deviation. *P < .05, ** P < .01, ***P < .001.