Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Leflunomide Inhibits rat-to-Mouse Cardiac Xenograft Rejection by Suppressing Adaptive Immune Cell Response and NF-κB Signaling Activation

Ma, Yunhan LU ; Xie, Baiyi ; Guo, Junjun ; Chen, Yingyu ; Zhong, Mengya ; Lin, Qingru ; Hua, Jianyu ; Zhong, Jiaying ; Luo, Xuewei and Yan, Guoliang , et al. (2021) In Cell Transplantation 30.
Abstract

Xenotransplantation is a potential solution for the severe shortage of human donor organs and tissues. The generation of humanized animal models attenuates strong innate immune responses, such as complement-mediated hyperacute rejection. However, acute vascular rejection and cell mediated rejection remain primary barriers to xenotransplantation, which limits its clinical application. In this study, we systematically investigated the immunosuppressive effect of LEF using a rat-to-mouse heart xenotransplantation model. SD rat xenogeneic hearts were transplanted into C57BL/6 mice, and survived 34.5 days after LEF treatment. In contrast, BALB/c allogeneic hearts were transplanted into C57BL/6 mice, and survived 31 days after LEF treatment.... (More)

Xenotransplantation is a potential solution for the severe shortage of human donor organs and tissues. The generation of humanized animal models attenuates strong innate immune responses, such as complement-mediated hyperacute rejection. However, acute vascular rejection and cell mediated rejection remain primary barriers to xenotransplantation, which limits its clinical application. In this study, we systematically investigated the immunosuppressive effect of LEF using a rat-to-mouse heart xenotransplantation model. SD rat xenogeneic hearts were transplanted into C57BL/6 mice, and survived 34.5 days after LEF treatment. In contrast, BALB/c allogeneic hearts were transplanted into C57BL/6 mice, and survived 31 days after LEF treatment. Compared to normal saline treatment, LEF treatment decreased xenoreactive T cells and CD19+ B cells in recipient splenocytes. Most importantly, LEF treatment protected myocardial cells by decreasing xenoreactive T and B cell infiltration, inflammatory gene expression, and IgM deposition in grafts. In vivo assays revealed that LEF treatment eliminated xenoreactive and alloreactive T and B lymphocytes by suppressing the activation of the NF-κB signaling pathway. Taken together, these observations complement the evidence supporting the potential use of LEF in xenotransplantation.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
heart transplant, T cell biology and B cell biology, xenotransplantation
in
Cell Transplantation
volume
30
publisher
Cognizant Communication Corporation
external identifiers
  • scopus:85120456848
  • pmid:34814739
ISSN
0963-6897
DOI
10.1177/09636897211054503
language
English
LU publication?
yes
id
decc39c9-5f8e-4091-96b3-70cb75040052
date added to LUP
2022-01-19 16:09:59
date last changed
2024-06-17 02:46:52
@article{decc39c9-5f8e-4091-96b3-70cb75040052,
  abstract     = {{<p>Xenotransplantation is a potential solution for the severe shortage of human donor organs and tissues. The generation of humanized animal models attenuates strong innate immune responses, such as complement-mediated hyperacute rejection. However, acute vascular rejection and cell mediated rejection remain primary barriers to xenotransplantation, which limits its clinical application. In this study, we systematically investigated the immunosuppressive effect of LEF using a rat-to-mouse heart xenotransplantation model. SD rat xenogeneic hearts were transplanted into C57BL/6 mice, and survived 34.5 days after LEF treatment. In contrast, BALB/c allogeneic hearts were transplanted into C57BL/6 mice, and survived 31 days after LEF treatment. Compared to normal saline treatment, LEF treatment decreased xenoreactive T cells and CD19<sup>+</sup> B cells in recipient splenocytes. Most importantly, LEF treatment protected myocardial cells by decreasing xenoreactive T and B cell infiltration, inflammatory gene expression, and IgM deposition in grafts. In vivo assays revealed that LEF treatment eliminated xenoreactive and alloreactive T and B lymphocytes by suppressing the activation of the NF-κB signaling pathway. Taken together, these observations complement the evidence supporting the potential use of LEF in xenotransplantation.</p>}},
  author       = {{Ma, Yunhan and Xie, Baiyi and Guo, Junjun and Chen, Yingyu and Zhong, Mengya and Lin, Qingru and Hua, Jianyu and Zhong, Jiaying and Luo, Xuewei and Yan, Guoliang and Dai, Helong and Qi, Zhongquan}},
  issn         = {{0963-6897}},
  keywords     = {{heart transplant; T cell biology and B cell biology; xenotransplantation}},
  language     = {{eng}},
  publisher    = {{Cognizant Communication Corporation}},
  series       = {{Cell Transplantation}},
  title        = {{Leflunomide Inhibits rat-to-Mouse Cardiac Xenograft Rejection by Suppressing Adaptive Immune Cell Response and NF-κB Signaling Activation}},
  url          = {{http://dx.doi.org/10.1177/09636897211054503}},
  doi          = {{10.1177/09636897211054503}},
  volume       = {{30}},
  year         = {{2021}},
}