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Complement component 3 deficiency prolongs MHC-II disparate skin allograft survival by increasing the CD4(+) CD25(+) regulatory T cells population

Recent reports suggest that complement system contributes to allograft rejection. However, its underlying mechanism is poorly understood. Herein, we investigate the role of complement component 3 (C3) in a single MHC-II molecule mismatched murine model of allograft rejection using C3 deficient mice...

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Autores principales: Zheng, Quan-you, Liang, Shen-ju, Li, Gui-qing, Lv, Yan-bo, Li, You, Tang, Ming, Zhang, Kun, Xu, Gui-lian, Zhang, Ke-qin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027598/
https://www.ncbi.nlm.nih.gov/pubmed/27641978
http://dx.doi.org/10.1038/srep33489
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author Zheng, Quan-you
Liang, Shen-ju
Li, Gui-qing
Lv, Yan-bo
Li, You
Tang, Ming
Zhang, Kun
Xu, Gui-lian
Zhang, Ke-qin
author_facet Zheng, Quan-you
Liang, Shen-ju
Li, Gui-qing
Lv, Yan-bo
Li, You
Tang, Ming
Zhang, Kun
Xu, Gui-lian
Zhang, Ke-qin
author_sort Zheng, Quan-you
collection PubMed
description Recent reports suggest that complement system contributes to allograft rejection. However, its underlying mechanism is poorly understood. Herein, we investigate the role of complement component 3 (C3) in a single MHC-II molecule mismatched murine model of allograft rejection using C3 deficient mice (C3(−/−)) as skin graft donors or recipients. Compared with C3(+/+) B6 allografts, C3(−/−) B6 grafts dramatically prolonged survival in MHC-II molecule mismatched H-2(bm12) B6 recipients, indicating that C3 plays a critical role in allograft rejection. Compared with C3(+/+) allografts, both Th17 cell infiltration and Th1/Th17 associated cytokine mRNA levels were clearly reduced in C3(−/−) allografts. Moreover, C3(−/−) allografts caused attenuated Th1/Th17 responses, but increased CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cell expression markedly in local intragraft and H-2(bm12) recipients. Depletion of Treg cells by anti-CD25 monoclonal antibody (mAb) negated the survival advantages conferred by C3 deficiency. Our results indicate for the first time that C3 deficiency can prolong MHC-II molecule mismatched skin allograft survival, which is further confirmed to be associated with increased CD4(+) CD25(+) Treg cell population expansion and attenuated Th1/Th17 response.
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spelling pubmed-50275982016-09-22 Complement component 3 deficiency prolongs MHC-II disparate skin allograft survival by increasing the CD4(+) CD25(+) regulatory T cells population Zheng, Quan-you Liang, Shen-ju Li, Gui-qing Lv, Yan-bo Li, You Tang, Ming Zhang, Kun Xu, Gui-lian Zhang, Ke-qin Sci Rep Article Recent reports suggest that complement system contributes to allograft rejection. However, its underlying mechanism is poorly understood. Herein, we investigate the role of complement component 3 (C3) in a single MHC-II molecule mismatched murine model of allograft rejection using C3 deficient mice (C3(−/−)) as skin graft donors or recipients. Compared with C3(+/+) B6 allografts, C3(−/−) B6 grafts dramatically prolonged survival in MHC-II molecule mismatched H-2(bm12) B6 recipients, indicating that C3 plays a critical role in allograft rejection. Compared with C3(+/+) allografts, both Th17 cell infiltration and Th1/Th17 associated cytokine mRNA levels were clearly reduced in C3(−/−) allografts. Moreover, C3(−/−) allografts caused attenuated Th1/Th17 responses, but increased CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cell expression markedly in local intragraft and H-2(bm12) recipients. Depletion of Treg cells by anti-CD25 monoclonal antibody (mAb) negated the survival advantages conferred by C3 deficiency. Our results indicate for the first time that C3 deficiency can prolong MHC-II molecule mismatched skin allograft survival, which is further confirmed to be associated with increased CD4(+) CD25(+) Treg cell population expansion and attenuated Th1/Th17 response. Nature Publishing Group 2016-09-19 /pmc/articles/PMC5027598/ /pubmed/27641978 http://dx.doi.org/10.1038/srep33489 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Zheng, Quan-you
Liang, Shen-ju
Li, Gui-qing
Lv, Yan-bo
Li, You
Tang, Ming
Zhang, Kun
Xu, Gui-lian
Zhang, Ke-qin
Complement component 3 deficiency prolongs MHC-II disparate skin allograft survival by increasing the CD4(+) CD25(+) regulatory T cells population
title Complement component 3 deficiency prolongs MHC-II disparate skin allograft survival by increasing the CD4(+) CD25(+) regulatory T cells population
title_full Complement component 3 deficiency prolongs MHC-II disparate skin allograft survival by increasing the CD4(+) CD25(+) regulatory T cells population
title_fullStr Complement component 3 deficiency prolongs MHC-II disparate skin allograft survival by increasing the CD4(+) CD25(+) regulatory T cells population
title_full_unstemmed Complement component 3 deficiency prolongs MHC-II disparate skin allograft survival by increasing the CD4(+) CD25(+) regulatory T cells population
title_short Complement component 3 deficiency prolongs MHC-II disparate skin allograft survival by increasing the CD4(+) CD25(+) regulatory T cells population
title_sort complement component 3 deficiency prolongs mhc-ii disparate skin allograft survival by increasing the cd4(+) cd25(+) regulatory t cells population
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027598/
https://www.ncbi.nlm.nih.gov/pubmed/27641978
http://dx.doi.org/10.1038/srep33489
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