Blockade of IL-6/IL-6R Signaling Attenuates Acute Antibody-Mediated Rejection in a Mouse Cardiac Transplantation Model

Acute antibody-mediated rejection (AAMR) is an important cause of cardiac allograft dysfunction, and more effective strategies need to be explored to improve allograft prognosis. Interleukin (IL)-6/IL-6R signaling plays a key role in the activation of immune cells including B cells, T cells and macr...

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Autores principales:	Maolin Ma, Qipeng Sun, Xiujie Li, Gengguo Deng, Yannan Zhang, Zhe Yang, Fei Han, Zhengyu Huang, Youqiang Fang, Tao Liao, Qiquan Sun
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	antibody-mediated rejection IL-6 IL-6R mouse model cardiac transplantation Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/6c72b2a0905a448894ce4f8dc24281b1
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spelling	oai:doaj.org-article:6c72b2a0905a448894ce4f8dc24281b12021-11-18T12:25:53ZBlockade of IL-6/IL-6R Signaling Attenuates Acute Antibody-Mediated Rejection in a Mouse Cardiac Transplantation Model1664-322410.3389/fimmu.2021.778359https://doaj.org/article/6c72b2a0905a448894ce4f8dc24281b12021-10-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.778359/fullhttps://doaj.org/toc/1664-3224Acute antibody-mediated rejection (AAMR) is an important cause of cardiac allograft dysfunction, and more effective strategies need to be explored to improve allograft prognosis. Interleukin (IL)-6/IL-6R signaling plays a key role in the activation of immune cells including B cells, T cells and macrophages, which participate in the progression of AAMR. In this study, we investigated the effect of IL-6/IL-6R signaling blockade on the prevention of AAMR in a mouse model. We established a mouse model of AAMR for cardiac transplantation via presensitization of skin grafts and addition of cyclosporin A, and sequentially analyzed its features. Tocilizumab, anti-IL-6R antibody, and recipient IL-6 knockout were used to block IL-6/IL-6R signaling. We demonstrated that blockade of IL-6/IL-6R signaling significantly attenuated allograft injury and improved survival. Further mechanistic research revealed that signaling blockade decreased B cells in circulation, spleens, and allografts, thus inhibiting donor-specific antibody production and complement activation. Moreover, macrophage, T cell, and pro-inflammatory cytokine infiltration in allografts was also reduced. Collectively, we provided a highly practical mouse model of AAMR and demonstrated that blockade of IL-6/IL-6R signaling markedly alleviated AAMR, which is expected to provide a superior option for the treatment of AAMR in clinic.Maolin MaQipeng SunXiujie LiGengguo DengYannan ZhangZhe YangFei HanZhengyu HuangYouqiang FangTao LiaoQiquan SunFrontiers Media S.A.articleantibody-mediated rejectionIL-6IL-6Rmouse modelcardiac transplantationImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	antibody-mediated rejection IL-6 IL-6R mouse model cardiac transplantation Immunologic diseases. Allergy RC581-607
spellingShingle	antibody-mediated rejection IL-6 IL-6R mouse model cardiac transplantation Immunologic diseases. Allergy RC581-607 Maolin Ma Qipeng Sun Xiujie Li Gengguo Deng Yannan Zhang Zhe Yang Fei Han Zhengyu Huang Youqiang Fang Tao Liao Qiquan Sun Blockade of IL-6/IL-6R Signaling Attenuates Acute Antibody-Mediated Rejection in a Mouse Cardiac Transplantation Model
description	Acute antibody-mediated rejection (AAMR) is an important cause of cardiac allograft dysfunction, and more effective strategies need to be explored to improve allograft prognosis. Interleukin (IL)-6/IL-6R signaling plays a key role in the activation of immune cells including B cells, T cells and macrophages, which participate in the progression of AAMR. In this study, we investigated the effect of IL-6/IL-6R signaling blockade on the prevention of AAMR in a mouse model. We established a mouse model of AAMR for cardiac transplantation via presensitization of skin grafts and addition of cyclosporin A, and sequentially analyzed its features. Tocilizumab, anti-IL-6R antibody, and recipient IL-6 knockout were used to block IL-6/IL-6R signaling. We demonstrated that blockade of IL-6/IL-6R signaling significantly attenuated allograft injury and improved survival. Further mechanistic research revealed that signaling blockade decreased B cells in circulation, spleens, and allografts, thus inhibiting donor-specific antibody production and complement activation. Moreover, macrophage, T cell, and pro-inflammatory cytokine infiltration in allografts was also reduced. Collectively, we provided a highly practical mouse model of AAMR and demonstrated that blockade of IL-6/IL-6R signaling markedly alleviated AAMR, which is expected to provide a superior option for the treatment of AAMR in clinic.
format	article
author	Maolin Ma Qipeng Sun Xiujie Li Gengguo Deng Yannan Zhang Zhe Yang Fei Han Zhengyu Huang Youqiang Fang Tao Liao Qiquan Sun
author_facet	Maolin Ma Qipeng Sun Xiujie Li Gengguo Deng Yannan Zhang Zhe Yang Fei Han Zhengyu Huang Youqiang Fang Tao Liao Qiquan Sun
author_sort	Maolin Ma
title	Blockade of IL-6/IL-6R Signaling Attenuates Acute Antibody-Mediated Rejection in a Mouse Cardiac Transplantation Model
title_short	Blockade of IL-6/IL-6R Signaling Attenuates Acute Antibody-Mediated Rejection in a Mouse Cardiac Transplantation Model
title_full	Blockade of IL-6/IL-6R Signaling Attenuates Acute Antibody-Mediated Rejection in a Mouse Cardiac Transplantation Model
title_fullStr	Blockade of IL-6/IL-6R Signaling Attenuates Acute Antibody-Mediated Rejection in a Mouse Cardiac Transplantation Model
title_full_unstemmed	Blockade of IL-6/IL-6R Signaling Attenuates Acute Antibody-Mediated Rejection in a Mouse Cardiac Transplantation Model
title_sort	blockade of il-6/il-6r signaling attenuates acute antibody-mediated rejection in a mouse cardiac transplantation model
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6c72b2a0905a448894ce4f8dc24281b1
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Blockade of IL-6/IL-6R Signaling Attenuates Acute Antibody-Mediated Rejection in a Mouse Cardiac Transplantation Model

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