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Yunhan Ma. Picture.

Yunhan Ma

Yunhan Ma, visitng researcher

Yunhan Ma. Picture.

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

Author

  • Yunhan Ma
  • Baiyi Xie
  • Junjun Guo
  • Yingyu Chen
  • Mengya Zhong
  • Qingru Lin
  • Jianyu Hua
  • Jiaying Zhong
  • Xuewei Luo
  • Guoliang Yan
  • Helong Dai
  • Zhongquan Qi

Summary, in English

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.

Department/s

  • Diabetes - Islet Patophysiology

Publishing year

2021-11

Language

English

Publication/Series

Cell Transplantation

Volume

30

Document type

Journal article

Publisher

Cognizant Communication Corporation

Topic

  • Surgery

Keywords

  • heart transplant
  • T cell biology and B cell biology
  • xenotransplantation

Status

Published

Research group

  • Diabetes - Islet Patophysiology

ISBN/ISSN/Other

  • ISSN: 0963-6897