2. Academic Validation
  3. Cytosporone B (Csn-B), an NR4A1 agonist, attenuates acute cardiac allograft rejection by inducing differential apoptosis of CD4+T cells

Cytosporone B (Csn-B), an NR4A1 agonist, attenuates acute cardiac allograft rejection by inducing differential apoptosis of CD4+T cells

  • Int Immunopharmacol. 2022 Mar;104:108521. doi: 10.1016/j.intimp.2022.108521.
Xiangchao Ding 1,  Sheng Le 2,  Ke Wang 3,  Yunshu Su 1,  Shanshan Chen 4,  Chuangyan Wu 5,  Jiuling Chen 5,  Shanshan Chen 6,  Anchen Zhang 7,  Jiahong Xia 8
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
  • 2 Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 3 Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 4 Key Laboratory for Molecular Diagnosis of Hubei Province and Central Laboratory, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 5 Departments of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 6 Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • 7 Department of Cardiovascular Medicine, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: zac000000@163.com.
  • 8 Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: jiahong.xia@hust.edu.cn.
PMID: 35026656 DOI: 10.1016/j.intimp.2022.108521
Abstract

CD4+T cell-mediated acute rejection remains a major factor that affects the early survival of transplanted organs post-transplantation. Here, we reveal that nuclear receptor subfamily 4 Group A member 1 (Nr4A1) was upregulated during cardiac allograft rejection and that the increased Nr4A1 was primarily localized in intragraft-infiltrating CD4+T cells. Nr4A1 acts as a transcription factor with an important role in CD4+T cell Apoptosis, differentiation and T cell dysfunction, which indicates that Nr4A1 may play a critical role in transplant rejection. Cytosporone B (Csn-B) is a naturally occurring agonist of Nr4A1, and the role of Csn-B in the physiological process of cardiac rejection is poorly defined. This study constructed an acute rejection model of abdominal heterotopic cardiac transplantation in mice and investigated whether Csn-B could attenuate acute transplant rejection by modulating the CD4+T lymphocyte response. The results showed that Csn-B prolonged murine cardiac allograft survival and reduced inflammation in allografts. Subsequently, it was confirmed that Csn-B functions by inducing non-Treg Apoptosis and promoting Treg cell differentiation. Finally, we also confirmed that Csn-B attenuates acute rejection by directly targeting Nr4A1 in CD4+T cells. Our data suggest that Csn-B is a promising novel therapeutic approach for acute cardiac allograft rejection.

Keywords

Apoptosis; CD4+ T cells; Nr4A1; Regulatory T cells; Transplant rejection.

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