[Study of mechanisms dependent on interleukin-17 and their modulation in development of bronchiolitis obliterans...

Survival of lung transplant recipients is currently limited by the primary graft dysfunction, an acute phenomenon occurring within 72 hours after the transplantation, but also by the chronic rejection that appears more than one year later. IL-17 might be implicated in these two diseases. The heterotopic trachea transplantation in mice generates epithelial lesions mimicking the human pathology. Using this model, we show that IL-17 was crucially implicated in early, but not chronic lesions after transplantation. The main intragraft cellular sources of IL-17 are recipient-derived gammadelta T cells. However, the IL17-dependent lesions in our model are not mediated by a direct effect of IL-17 on donor-derived cells. Nevertheless, its inhibition protects CK-14+ basal epithelial stem cells that are known to be capable of renewing of the whole epithelium.