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Cyclic Helix B Peptide Prolongs Skin Allograft Survival via Inhibition of B Cell Immune Responses in a Murine Model

Antibody-mediated rejection (AMR) represents a major cause of allograft dysfunction and results in allograft failure in solid organ transplantation. Cyclic helix B peptide (CHBP) is a novel erythropoietin-derived peptide that ameliorated renal allograft rejection in a renal transplantation model. Ho...

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Autores principales: Zheng, Long, Wang, Xuanchuan, Hu, Linkun, Gao, Wenjun, Zhang, Weitao, Zhang, Xuepeng, Hu, Chao, Rong, Ruiming, Yang, Cheng, Zhu, Dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149941/
https://www.ncbi.nlm.nih.gov/pubmed/34054874
http://dx.doi.org/10.3389/fimmu.2021.682749
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author Zheng, Long
Wang, Xuanchuan
Hu, Linkun
Gao, Wenjun
Zhang, Weitao
Zhang, Xuepeng
Hu, Chao
Rong, Ruiming
Yang, Cheng
Zhu, Dong
author_facet Zheng, Long
Wang, Xuanchuan
Hu, Linkun
Gao, Wenjun
Zhang, Weitao
Zhang, Xuepeng
Hu, Chao
Rong, Ruiming
Yang, Cheng
Zhu, Dong
author_sort Zheng, Long
collection PubMed
description Antibody-mediated rejection (AMR) represents a major cause of allograft dysfunction and results in allograft failure in solid organ transplantation. Cyclic helix B peptide (CHBP) is a novel erythropoietin-derived peptide that ameliorated renal allograft rejection in a renal transplantation model. However, its effect on AMR remains unknown. This study aimed to investigate the effect of CHBP on AMR using a secondary allogeneic skin transplantation model, which was created by transplanting skin from BALB/c mice to C57BL/6 mice with or without CHBP treatment. A secondary syngeneic skin transplantation model, involving transplantation from C57BL/6 mice to C57BL/6 mice, was also created to act as a control. Skin graft rejection, CD19(+) B cell infiltration in the skin allograft, the percentages of splenic plasma cells, germinal center (GC) B cells, and Tfh cells, the serum levels of donor specific antibodies (DSAs), and NF-κB signaling in splenocytes were analyzed. Skin allograft survival was significantly prolonged in the CHBP group compared to the allogeneic group. CHBP treatment also significantly reduced the CD19(+) B cell infiltration in the skin allograft, decreased the percentages of splenic plasma cells, GC B cells, and Tfh cells, and ameliorated the increase in the serum DSA level. At a molecular level, CHBP downregulated P100, RelB, and P52 in splenocytes. CHBP prolonged skin allograft survival by inhibiting AMR, which may be mediated by inhibition of NF-κB signaling to suppress B cell immune responses, thereby decreasing the DSA level.
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spelling pubmed-81499412021-05-27 Cyclic Helix B Peptide Prolongs Skin Allograft Survival via Inhibition of B Cell Immune Responses in a Murine Model Zheng, Long Wang, Xuanchuan Hu, Linkun Gao, Wenjun Zhang, Weitao Zhang, Xuepeng Hu, Chao Rong, Ruiming Yang, Cheng Zhu, Dong Front Immunol Immunology Antibody-mediated rejection (AMR) represents a major cause of allograft dysfunction and results in allograft failure in solid organ transplantation. Cyclic helix B peptide (CHBP) is a novel erythropoietin-derived peptide that ameliorated renal allograft rejection in a renal transplantation model. However, its effect on AMR remains unknown. This study aimed to investigate the effect of CHBP on AMR using a secondary allogeneic skin transplantation model, which was created by transplanting skin from BALB/c mice to C57BL/6 mice with or without CHBP treatment. A secondary syngeneic skin transplantation model, involving transplantation from C57BL/6 mice to C57BL/6 mice, was also created to act as a control. Skin graft rejection, CD19(+) B cell infiltration in the skin allograft, the percentages of splenic plasma cells, germinal center (GC) B cells, and Tfh cells, the serum levels of donor specific antibodies (DSAs), and NF-κB signaling in splenocytes were analyzed. Skin allograft survival was significantly prolonged in the CHBP group compared to the allogeneic group. CHBP treatment also significantly reduced the CD19(+) B cell infiltration in the skin allograft, decreased the percentages of splenic plasma cells, GC B cells, and Tfh cells, and ameliorated the increase in the serum DSA level. At a molecular level, CHBP downregulated P100, RelB, and P52 in splenocytes. CHBP prolonged skin allograft survival by inhibiting AMR, which may be mediated by inhibition of NF-κB signaling to suppress B cell immune responses, thereby decreasing the DSA level. Frontiers Media S.A. 2021-05-12 /pmc/articles/PMC8149941/ /pubmed/34054874 http://dx.doi.org/10.3389/fimmu.2021.682749 Text en Copyright © 2021 Zheng, Wang, Hu, Gao, Zhang, Zhang, Hu, Rong, Yang and Zhu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zheng, Long
Wang, Xuanchuan
Hu, Linkun
Gao, Wenjun
Zhang, Weitao
Zhang, Xuepeng
Hu, Chao
Rong, Ruiming
Yang, Cheng
Zhu, Dong
Cyclic Helix B Peptide Prolongs Skin Allograft Survival via Inhibition of B Cell Immune Responses in a Murine Model
title Cyclic Helix B Peptide Prolongs Skin Allograft Survival via Inhibition of B Cell Immune Responses in a Murine Model
title_full Cyclic Helix B Peptide Prolongs Skin Allograft Survival via Inhibition of B Cell Immune Responses in a Murine Model
title_fullStr Cyclic Helix B Peptide Prolongs Skin Allograft Survival via Inhibition of B Cell Immune Responses in a Murine Model
title_full_unstemmed Cyclic Helix B Peptide Prolongs Skin Allograft Survival via Inhibition of B Cell Immune Responses in a Murine Model
title_short Cyclic Helix B Peptide Prolongs Skin Allograft Survival via Inhibition of B Cell Immune Responses in a Murine Model
title_sort cyclic helix b peptide prolongs skin allograft survival via inhibition of b cell immune responses in a murine model
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149941/
https://www.ncbi.nlm.nih.gov/pubmed/34054874
http://dx.doi.org/10.3389/fimmu.2021.682749
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