Chronic Rejection Lesions Are Decreased in IL-17 KO Mice after Orthotopic Lung Transplantation

Abstract

<h3>Purpose</h3> Long term survival after lung transplantation (LTx) is hampered by chronic rejection, histologically characterized by obliterative bronchiolitis (OB). A murine model of orthotopic lung transplantation showing OB, lymphocytic bronchiolitis (LB) and abnormal parenchyma has previously been established in our lab (De Vleeschauwer et al. 2012). Interleukin-17 (IL-17) is identified as potential player in the onset of chronic rejection. Aim: To investigate the role of IL-17 by using IL-17 knock out (KO) mice in our model. <h3>Methods and Materials</h3> Allografts are donor Balb/c lungs transplanted in C57Bl6 (wild type) receptors. Knock out allografts are donor Balb/c lungs transplanted in C57Bl6 IL-17 KO receptors (kindly provided by J. Kolls and Y. Iwakura). Isografts have donor lungs from mice genetically identical to the receptors. All allograft receptors received daily 10 mg/kg cyclosporine and 1.6 mg/kg methylprednisolone. Histopathological examination (H&E staining) was performed 10 weeks after surgery. <h3>Results</h3> Ten weeks after LTx, isografts (n=4) had a completely normal lung histology. Allografts (n=4) showed OB, LB and abnormal parenchyma as previously established in the model. In the IL-17 KO allograft (n=4), however, no OB lesions could be identified. LB lesions were still present, but less pronounced and lung parenchyma was almost normal. [figure 1] <h3>Conclusions</h3> Chronic rejection lesions (OB) are decreased in IL-17 KO mice, hereby providing the ultimate proof of involvement of IL-17 in the onset of chronic rejection after lung transplantation.