Transplantation: Transplantation |

Role of Interleukin-17A in Early Graft Rejection After Orthotopic Lung Transplantation in Mice FREE TO VIEW

Qirui Chen, MD
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Beijing Chao-yang Hospital, Beijing, China

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;149(4_S):A602. doi:10.1016/j.chest.2016.02.629
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SESSION TITLE: Transplantation

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM

PURPOSE: The cellular and molecular mechanisms underlying lung allograft rejection remain poorly understood, especially obliterative bronchiolitis (OB). We investigated the potential role of interleukin (IL)-17A in lung transplant rejection in a mouse model, because previous studies in clinical and rodent models have implicated IL-17A in both acute and chronic rejection.

METHODS: To generate an orthotopic lung transplantation model, lungs from C57BL/6 or BALB/c mice were transplanted into C57BL/6 mice (isograft and allograft models, respectively). The effects of anti-IL-17A treatment in allograft recipients were investigated. The histological features and rejection status of isografts and allografts were assessed at 3, 7, and 28 days after transplantation, and differences in graft infiltrating cells and mRNA expression of relevant cytokines were quantified at 3 and 7 days after transplantation.

RESULTS: As expected, isografts showed no obvious signs of rejection, whereas allografts exhibited minimal-to-mild rejection (grade A1-A2) by day 3 and moderate-to-severe rejection (grade A3-A4) by day 7, without evidence of OB. However, by 28 days, evidence of OB was observed in 67% (2/3) of allografts and severe rejection (grade A4) was observed in all. IL-17 mRNA expression in allografts was increased with rejection, and interferon-γ and IL-6 mRNA expression levels followed a similar pattern. In contrast, IL-22 expression in allografts was only slightly increased. Antibody neutralization of IL-17A diminished the signs of acute rejection at 7 days after transplantation in allografts, and this early protection was accompanied by a decrease in cellular stress according to histological evaluation, suggesting the involvement of IL-17A in the development of early post-transplantation lesions. Moreover, increased γδT lymphocyte infiltration, especially Vγ4 γδT cells, was observed in allografts and may represent a source of IL-17A post-transplantation.

CONCLUSIONS: Our data indicate that IL-17A is important in the pathophysiology of allograft rejection, and neutralization of IL-17A is a potential therapeutic strategy to preventing lung transplant rejection.

CLINICAL IMPLICATIONS: A better understanding of the cellular and molecular mechanisms of lung graft injury will be critical to improving survival among clinical lung transplant recipients.

DISCLOSURE: The following authors have nothing to disclose: Qirui Chen

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