49 - Freie Mitteilung
Clinical works II
16. Mai 2019, 10:15 - 11:45, Bellavista 2, 6. OG
CD26/DPP4 is overexpressed in experimental chronic lung allograft rejection and potentially qualifies as a target to reduce chronic rejection
W. Jungraithmayr1, L. Dubs2, F. Janker2, C. Opelz2, Y. Yamada2, W. Weder2, J. H. Jang2, Presenter: W. Jungraithmayr1 (1Rostock/DE, 2Zurich)
Chronic lung allograft dysfunction (CLAD) is the major obstacle for long term survival in lung transplant recipients. The transmembrane molecule CD26/dipeptidyl peptidase 4 (CD26) is known to be a surface marker of different fibrogenic stroma formation. Own data show that CD26 is co-expressed with TFG-b1 within the fibrotic stroma compartment of lung tumors. We therefore hypothesize if CD26 is expressed in a CLAD mouse lung transplant model rendering CD26-inhibition as a therapy against fibrosis.
We previously developed CLAD lesions in mouse lungs eight weeks after lung transplantation using BALB/c (donors) and C57BL/6 (recipients) under mild immunosuppression. Pro-fibrotic genes including IGF1, MMP9, CXCL9, IL6, and IL13 were analyzed by RT-qPCR. Protein levels of EMT-related genes including Vimentin, Ncadherin, Slug, and Hif1α were measured by western blotting, and immunohistochemistry (IHC) was employed to assess CD26 in transplants.
The development of CLAD lesions in mouse lungs was confirmed by a significantly higher expression of the EMT proteins Vimentin, Ncadherin, Slug, and Hif1α vs. normal lungs (p<0.05). Also, gene expression levels of IGF1, MMP9, and CXCL9 where significantly higher expressed in CLAD-developing lungs vs. normal lungs (p<0.05). In these CLAD lesions, the transmembrane molecule CD26 was significantly higher expressed in IHC vs. normal lungs (p=0.0003). In contrast, gene expression levels of IL6 and IL13 were significantly decreased vs. normal lungs (p<0.0001).
The increased expression of CD26 in chronically rejected lung allografts suggests that CD26 is a potential target to attenuate the development of CLAD lesions after transplantation.