Donor myeloid derived suppressor cells (MDSCs) prolong allogeneic cardiac graft survival through programming of recipient myeloid cells in vivo

Abstract Solid organ transplantation is a lifesaving therapy for patients with end-organ disease. Current immunosuppression protocols are not designed to target antigen-specific alloimmunity and are uncapable of preventing chronic allograft injury. As myeloid-derived suppressor cells (MDSCs) are pot...

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Autores principales:	Songjie Cai, John Y. Choi, Thiago J. Borges, Hengcheng Zhang, Ji Miao, Takaharu Ichimura, Xiaofei Li, Simiao Xu, Philip Chu, Siawosh K. Eskandari, Hazim Allos, Juliano B. Alhaddad, Saif A. Muhsin, Karim Yatim, Leonardo V. Riella, Peter T. Sage, Anil K. Chandraker, Jamil R. Azzi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/de36c318422d4c6c994a080dce4925be
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spelling	oai:doaj.org-article:de36c318422d4c6c994a080dce4925be2021-12-02T19:02:37ZDonor myeloid derived suppressor cells (MDSCs) prolong allogeneic cardiac graft survival through programming of recipient myeloid cells in vivo10.1038/s41598-020-71289-z2045-2322https://doaj.org/article/de36c318422d4c6c994a080dce4925be2020-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-71289-zhttps://doaj.org/toc/2045-2322Abstract Solid organ transplantation is a lifesaving therapy for patients with end-organ disease. Current immunosuppression protocols are not designed to target antigen-specific alloimmunity and are uncapable of preventing chronic allograft injury. As myeloid-derived suppressor cells (MDSCs) are potent immunoregulatory cells, we tested whether donor-derived MDSCs can protect heart transplant allografts in an antigen-specific manner. C57BL/6 (H2Kb, I-Ab) recipients pre-treated with BALB/c MDSCs were transplanted with either donor-type (BALB/c, H2Kd, I-Ad) or third-party (C3H, H2Kk, I-Ak) cardiac grafts. Spleens and allografts from C57BL/6 recipients were harvested for immune phenotyping, transcriptomic profiling and functional assays. Single injection of donor-derived MDSCs significantly prolonged the fully MHC mismatched allogeneic cardiac graft survival in a donor-specific fashion. Transcriptomic analysis of allografts harvested from donor-derived MDSCs treated recipients showed down-regulated proinflammatory cytokines. Immune phenotyping showed that the donor MDSCs administration suppressed effector T cells in recipients. Interestingly, significant increase in recipient endogenous CD11b+Gr1+ MDSC population was observed in the group treated with donor-derived MDSCs compared to the control groups. Depletion of this endogenous MDSCs with anti-Gr1 antibody reversed donor MDSCs-mediated allograft protection. Furthermore, we observed that the allogeneic mixed lymphocytes reaction was suppressed in the presence of CD11b+Gr1+ MDSCs in a donor-specific manner. Donor-derived MDSCs prolong cardiac allograft survival in a donor-specific manner via induction of recipient’s endogenous MDSCs.Songjie CaiJohn Y. ChoiThiago J. BorgesHengcheng ZhangJi MiaoTakaharu IchimuraXiaofei LiSimiao XuPhilip ChuSiawosh K. EskandariHazim AllosJuliano B. AlhaddadSaif A. MuhsinKarim YatimLeonardo V. RiellaPeter T. SageAnil K. ChandrakerJamil R. AzziNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Songjie Cai John Y. Choi Thiago J. Borges Hengcheng Zhang Ji Miao Takaharu Ichimura Xiaofei Li Simiao Xu Philip Chu Siawosh K. Eskandari Hazim Allos Juliano B. Alhaddad Saif A. Muhsin Karim Yatim Leonardo V. Riella Peter T. Sage Anil K. Chandraker Jamil R. Azzi Donor myeloid derived suppressor cells (MDSCs) prolong allogeneic cardiac graft survival through programming of recipient myeloid cells in vivo
description	Abstract Solid organ transplantation is a lifesaving therapy for patients with end-organ disease. Current immunosuppression protocols are not designed to target antigen-specific alloimmunity and are uncapable of preventing chronic allograft injury. As myeloid-derived suppressor cells (MDSCs) are potent immunoregulatory cells, we tested whether donor-derived MDSCs can protect heart transplant allografts in an antigen-specific manner. C57BL/6 (H2Kb, I-Ab) recipients pre-treated with BALB/c MDSCs were transplanted with either donor-type (BALB/c, H2Kd, I-Ad) or third-party (C3H, H2Kk, I-Ak) cardiac grafts. Spleens and allografts from C57BL/6 recipients were harvested for immune phenotyping, transcriptomic profiling and functional assays. Single injection of donor-derived MDSCs significantly prolonged the fully MHC mismatched allogeneic cardiac graft survival in a donor-specific fashion. Transcriptomic analysis of allografts harvested from donor-derived MDSCs treated recipients showed down-regulated proinflammatory cytokines. Immune phenotyping showed that the donor MDSCs administration suppressed effector T cells in recipients. Interestingly, significant increase in recipient endogenous CD11b+Gr1+ MDSC population was observed in the group treated with donor-derived MDSCs compared to the control groups. Depletion of this endogenous MDSCs with anti-Gr1 antibody reversed donor MDSCs-mediated allograft protection. Furthermore, we observed that the allogeneic mixed lymphocytes reaction was suppressed in the presence of CD11b+Gr1+ MDSCs in a donor-specific manner. Donor-derived MDSCs prolong cardiac allograft survival in a donor-specific manner via induction of recipient’s endogenous MDSCs.
format	article
author	Songjie Cai John Y. Choi Thiago J. Borges Hengcheng Zhang Ji Miao Takaharu Ichimura Xiaofei Li Simiao Xu Philip Chu Siawosh K. Eskandari Hazim Allos Juliano B. Alhaddad Saif A. Muhsin Karim Yatim Leonardo V. Riella Peter T. Sage Anil K. Chandraker Jamil R. Azzi
author_facet	Songjie Cai John Y. Choi Thiago J. Borges Hengcheng Zhang Ji Miao Takaharu Ichimura Xiaofei Li Simiao Xu Philip Chu Siawosh K. Eskandari Hazim Allos Juliano B. Alhaddad Saif A. Muhsin Karim Yatim Leonardo V. Riella Peter T. Sage Anil K. Chandraker Jamil R. Azzi
author_sort	Songjie Cai
title	Donor myeloid derived suppressor cells (MDSCs) prolong allogeneic cardiac graft survival through programming of recipient myeloid cells in vivo
title_short	Donor myeloid derived suppressor cells (MDSCs) prolong allogeneic cardiac graft survival through programming of recipient myeloid cells in vivo
title_full	Donor myeloid derived suppressor cells (MDSCs) prolong allogeneic cardiac graft survival through programming of recipient myeloid cells in vivo
title_fullStr	Donor myeloid derived suppressor cells (MDSCs) prolong allogeneic cardiac graft survival through programming of recipient myeloid cells in vivo
title_full_unstemmed	Donor myeloid derived suppressor cells (MDSCs) prolong allogeneic cardiac graft survival through programming of recipient myeloid cells in vivo
title_sort	donor myeloid derived suppressor cells (mdscs) prolong allogeneic cardiac graft survival through programming of recipient myeloid cells in vivo
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/de36c318422d4c6c994a080dce4925be
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Donor myeloid derived suppressor cells (MDSCs) prolong allogeneic cardiac graft survival through programming of recipient myeloid cells in vivo

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