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

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...

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Autores principales:	Yunhan Ma, Baiyi Xie, Junjun Guo, Yingyu Chen, Mengya Zhong, Qingru Lin, Jianyu Hua, Jiaying Zhong, Xuewei Luo, Guoliang Yan, Helong Dai, Zhongquan Qi
Formato:	article
Lenguaje:	EN
Publicado:	SAGE Publishing 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/0b8064bd5a1c498f85293c37590d46d2
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spelling	oai:doaj.org-article:0b8064bd5a1c498f85293c37590d46d22021-12-02T01:33:57ZLeflunomide Inhibits rat-to-Mouse Cardiac Xenograft Rejection by Suppressing Adaptive Immune Cell Response and NF-κB Signaling Activation1555-389210.1177/09636897211054503https://doaj.org/article/0b8064bd5a1c498f85293c37590d46d22021-11-01T00:00:00Zhttps://doi.org/10.1177/09636897211054503https://doaj.org/toc/1555-3892Xenotransplantation 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.Yunhan MaBaiyi XieJunjun GuoYingyu ChenMengya ZhongQingru LinJianyu HuaJiaying ZhongXuewei LuoGuoliang YanHelong DaiZhongquan QiSAGE PublishingarticleMedicineRENCell Transplantation, Vol 30 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R Yunhan Ma Baiyi Xie Junjun Guo Yingyu Chen Mengya Zhong Qingru Lin Jianyu Hua Jiaying Zhong Xuewei Luo Guoliang Yan Helong Dai Zhongquan Qi Leflunomide Inhibits rat-to-Mouse Cardiac Xenograft Rejection by Suppressing Adaptive Immune Cell Response and NF-κB Signaling Activation
description	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.
format	article
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
author_facet	Yunhan Ma Baiyi Xie Junjun Guo Yingyu Chen Mengya Zhong Qingru Lin Jianyu Hua Jiaying Zhong Xuewei Luo Guoliang Yan Helong Dai Zhongquan Qi
author_sort	Yunhan Ma
title	Leflunomide Inhibits rat-to-Mouse Cardiac Xenograft Rejection by Suppressing Adaptive Immune Cell Response and NF-κB Signaling Activation
title_short	Leflunomide Inhibits rat-to-Mouse Cardiac Xenograft Rejection by Suppressing Adaptive Immune Cell Response and NF-κB Signaling Activation
title_full	Leflunomide Inhibits rat-to-Mouse Cardiac Xenograft Rejection by Suppressing Adaptive Immune Cell Response and NF-κB Signaling Activation
title_fullStr	Leflunomide Inhibits rat-to-Mouse Cardiac Xenograft Rejection by Suppressing Adaptive Immune Cell Response and NF-κB Signaling Activation
title_full_unstemmed	Leflunomide Inhibits rat-to-Mouse Cardiac Xenograft Rejection by Suppressing Adaptive Immune Cell Response and NF-κB Signaling Activation
title_sort	leflunomide inhibits rat-to-mouse cardiac xenograft rejection by suppressing adaptive immune cell response and nf-κb signaling activation
publisher	SAGE Publishing
publishDate	2021
url	https://doaj.org/article/0b8064bd5a1c498f85293c37590d46d2
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Leflunomide Inhibits rat-to-Mouse Cardiac Xenograft Rejection by Suppressing Adaptive Immune Cell Response and NF-κB Signaling Activation

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