Pioglitazone Induces Infiltrations of Regulatory T Cells in the Tracheal Graft and Attenuates Allograft Rejection

Purpose Bronchiolitis obliterans (BO) and bronchiolitis obliterans syndrome were recognized as serious complications after lung transplantation. We hypothesized that pioglitazone, a peroxisome proliferator-activated receptor (PPAR)-γ agonist, could prevent airway rejection in established mouse orthotopic tracheal transplant models. Methods Tracheal grafts from wild type BALB/c or C57BL/6 were transplanted to C57BL/6 recipients. Experimental groups were treated with multiple doses of pioglitazone, at total 5mg/kg per day. Histopathologic evaluation of luminal obliteration was blindly reviewed at day 7. Immunohistochemistry for CD3, FoxP3 and real-time PCR analyses for cytokines were performed. Results Allografts treated with pioglitazone revealed a striking reduction of thickening in airway layers (P Conclusion Pioglitazone leads to decreased airway graft luminal occlusion and induced accumulation of Tregs in the graft. These data indicated a strong protective role for pioglitazone against BO. The potential mechanism of this beneficial effect of pioglitazone appears to increase the production of IL-4 and decrease the production of IFN-γ, TNF-α and IL-6.