Halofuginone treatment reduces interleukin-17A and ameliorates features of chronic lung allograft dysfunction in a mouse orthotopic lung transplant model

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
Hisashi OishiShaf Keshavjee

Abstract

Increasing evidence suggests that interleukin (IL)-17A plays an important role in chronic lung allograft dysfunction (CLAD), characterized by airway and lung parenchymal fibrosis, after lung transplantation. Halofuginone is a plant derivative that has been shown to inhibit Th17 differentiation. The purpose of this study was to examine the effect of halofuginone on CLAD development using a minor alloantigen‒mismatched mouse orthotopic lung transplant model. C57BL/6 recipient mice received an orthotopic left lung transplant from C57BL/10 donors, mismatched for minor antigens. Lung transplant recipients received daily intraperitoneal injections of 2.5 μg halofuginone or vehicle alone. Lung grafts were assessed on Days 7, 14, and 28 post-transplant. Compared with control mice, on Day 28 post-transplant, lung grafts of mice treated with halofuginone showed a significant reduction in the percentage of obliterated airways (6.8 ± 4.7% vs 52.5 ± 13.8%, p < 0.01), as well as significantly reduced parenchymal fibrosis (5.5 ± 2.3% vs 35.9 ± 10.9%, p < 0.05). Immunofluorescent staining for IL-17A demonstrated a decreased number and frequency of IL-17A‒positive cells in halofuginone-treated lung grafts on Day 28, as compared with controls. H...Continue Reading

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Citations

May 24, 2016·Chest·Stijn E VerledenGeert M Verleden
Jan 25, 2017·American Journal of Respiratory Cell and Molecular Biology·Pawan Kumar GuptaRebecca A Shilling
Nov 1, 2018·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Tereza MartinuShaf Keshavjee
Aug 1, 2019·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Tatsuaki WatanabeStephen C Juvet
Jan 17, 2017·Current Transplantation Reports·Jason M GauthierDaniel Kreisel
Apr 8, 2020·Proceedings of the National Academy of Sciences of the United States of America·Yeonjin KimTracy L Keller
Mar 7, 2019·Journal of the Chinese Medical Association : JCMA·Bin HeHui-Min Chu

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