Faculty Collaboration Database

Lentivirus IL-10 gene therapy down-regulates IL-17 and attenuates mouse orthotopic lung allograft rejection. Am J Transplant 2013 Jun;13(6):1586-93

Date

04/23/2013

Pubmed ID

23601206

DOI

10.1111/ajt.12230

Scopus ID

2-s2.0-84878503027 (requires institutional sign-in at Scopus site)   41 Citations

Abstract

The purpose of the study was to examine the effect of lentivirus-mediated IL-10 gene therapy to target lung allograft rejection in a mouse orthotopic left lung transplantation model. IL-10 may regulate posttransplant immunity mediated by IL-17. Lentivirus-mediated trans-airway luciferase gene transfer to the donor lung resulted in persistent luciferase activity up to 6 months posttransplant in the isograft (B6 to B6); luciferase activity decreased in minor-mismatched allograft lungs (B10 to B6) in association with moderate rejection. Fully MHC-mismatched allograft transplantation (BALB/c to B6) resulted in severe rejection and complete loss of luciferase activity. In minor-mismatched allografts, IL-10-encoding lentivirus gene therapy reduced the acute rejection score compared with the lentivirus-luciferase control at posttransplant day 28 (3.0 ± 0.6 vs. 2.0 ± 0.6 (mean ± SD); p = 0.025; n = 6/group). IL-10 gene therapy also significantly reduced gene expression of IL-17, IL-23, and retinoic acid-related orphan receptor (ROR)-γt without affecting levels of IL-12 and interferon-γ (IFN-γ). Cells expressing IL-17 were dramatically reduced in the allograft lung. In conclusion, lentivirus-mediated IL-10 gene therapy significantly reduced expression of IL-17 and other associated genes in the transplanted allograft lung and attenuated posttransplant immune responses after orthotopic lung transplantation.

Author List

Hirayama S, Sato M, Loisel-Meyer S, Matsuda Y, Oishi H, Guan Z, Saito T, Yeung J, Cypel M, Hwang DM, Medin JA, Liu M, Keshavjee S

Author

Jeffrey A. Medin PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Disease Models, Animal
Down-Regulation
Female
Genetic Therapy
Graft Rejection
Graft Survival
Interleukin-10
Interleukin-17
Lentivirus
Lung Transplantation
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
RNA
Real-Time Polymerase Chain Reaction
Transplantation, Homologous