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Phosphorylcholine-Primed Dendritic Cells Aggravate the Development of Atherosclerosis in ApoE(−/−) Mice

Background: Atherosclerosis is an inflammatory disease involving activation of adaptive and innate immune responses to antigens, including oxidized low-density lipoprotein (oxLDL) and phosphorylcholine (PC). Dendritic cells (DCs), which are antigen-presenting cells that activate T cells, are present...

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Autores principales: Dong, Qian, Yu, Jian, Ding, Yan, Ji, Qing-Wei, Zhu, Rui-Rui, Wei, Yu-Zhen, Xu, Wen-Bing, Zhong, Yu-Cheng, Zhu, Zheng-Feng, Meng, Kai, Peng, Yu-Dong, Sun, Hai-Tao, Wang, Yue, Pan, Cheng-Liang, Zeng, Qiu-Tang, Yu, Kun-Wu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Japanese Circulation Society 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939956/
https://www.ncbi.nlm.nih.gov/pubmed/33693294
http://dx.doi.org/10.1253/circrep.CR-20-0118
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author Dong, Qian
Yu, Jian
Ding, Yan
Ji, Qing-Wei
Zhu, Rui-Rui
Wei, Yu-Zhen
Xu, Wen-Bing
Zhong, Yu-Cheng
Zhu, Zheng-Feng
Meng, Kai
Peng, Yu-Dong
Sun, Hai-Tao
Wang, Yue
Pan, Cheng-Liang
Zeng, Qiu-Tang
Yu, Kun-Wu
author_facet Dong, Qian
Yu, Jian
Ding, Yan
Ji, Qing-Wei
Zhu, Rui-Rui
Wei, Yu-Zhen
Xu, Wen-Bing
Zhong, Yu-Cheng
Zhu, Zheng-Feng
Meng, Kai
Peng, Yu-Dong
Sun, Hai-Tao
Wang, Yue
Pan, Cheng-Liang
Zeng, Qiu-Tang
Yu, Kun-Wu
author_sort Dong, Qian
collection PubMed
description Background: Atherosclerosis is an inflammatory disease involving activation of adaptive and innate immune responses to antigens, including oxidized low-density lipoprotein (oxLDL) and phosphorylcholine (PC). Dendritic cells (DCs), which are antigen-presenting cells that activate T cells, are present in atherosclerotic lesions and are activated in immune organs. However, the mechanism by which PC promotes atherosclerosis is unclear. Methods and Results: To evaluate whether PC promotes atherosclerosis via DCs, 2×10(5) DCs activated by PC-keyhole limpet hemocyanin (DCs+PC-KLH) were injected into ApoE(−/−) mice and the features of the plaques and the effects of the DCs on cellular and humoral immunity against PC-KLH were determined. Mice injected with DCs+PC-KLH had significantly larger atherosclerotic lesions than controls, with increased inflammation in the lesions and plaque instability. Furthermore, DCs+PC-KLH were characterized using flow cytometry after coculture of bone marrow-derived DCs and naïve T cells. DCs+PC-KLH showed an inflammatory phenotype, with increased CD86, CD40, and major histocompatibility complex Class II molecules (MHC-II), which promoted PC-specific T helper (Th) 1 and Th17 cell differentiation in vivo and in vitro. Moreover, 2 weeks after the administration of DCs+PC-KLH to mice, these mice produced PC- and oxLDL-specific IgG2a, compared with no production in the controls. Conclusions: These findings suggest that DCs presenting PC promote specific immunity to PC, increase lesion inflammation, and accelerate atherosclerosis, which may explain how PC promotes atherosclerosis.
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spelling pubmed-79399562021-03-09 Phosphorylcholine-Primed Dendritic Cells Aggravate the Development of Atherosclerosis in ApoE(−/−) Mice Dong, Qian Yu, Jian Ding, Yan Ji, Qing-Wei Zhu, Rui-Rui Wei, Yu-Zhen Xu, Wen-Bing Zhong, Yu-Cheng Zhu, Zheng-Feng Meng, Kai Peng, Yu-Dong Sun, Hai-Tao Wang, Yue Pan, Cheng-Liang Zeng, Qiu-Tang Yu, Kun-Wu Circ Rep Original article Background: Atherosclerosis is an inflammatory disease involving activation of adaptive and innate immune responses to antigens, including oxidized low-density lipoprotein (oxLDL) and phosphorylcholine (PC). Dendritic cells (DCs), which are antigen-presenting cells that activate T cells, are present in atherosclerotic lesions and are activated in immune organs. However, the mechanism by which PC promotes atherosclerosis is unclear. Methods and Results: To evaluate whether PC promotes atherosclerosis via DCs, 2×10(5) DCs activated by PC-keyhole limpet hemocyanin (DCs+PC-KLH) were injected into ApoE(−/−) mice and the features of the plaques and the effects of the DCs on cellular and humoral immunity against PC-KLH were determined. Mice injected with DCs+PC-KLH had significantly larger atherosclerotic lesions than controls, with increased inflammation in the lesions and plaque instability. Furthermore, DCs+PC-KLH were characterized using flow cytometry after coculture of bone marrow-derived DCs and naïve T cells. DCs+PC-KLH showed an inflammatory phenotype, with increased CD86, CD40, and major histocompatibility complex Class II molecules (MHC-II), which promoted PC-specific T helper (Th) 1 and Th17 cell differentiation in vivo and in vitro. Moreover, 2 weeks after the administration of DCs+PC-KLH to mice, these mice produced PC- and oxLDL-specific IgG2a, compared with no production in the controls. Conclusions: These findings suggest that DCs presenting PC promote specific immunity to PC, increase lesion inflammation, and accelerate atherosclerosis, which may explain how PC promotes atherosclerosis. The Japanese Circulation Society 2021-01-16 /pmc/articles/PMC7939956/ /pubmed/33693294 http://dx.doi.org/10.1253/circrep.CR-20-0118 Text en Copyright © 2021, THE JAPANESE CIRCULATION SOCIETY This article is licensed under a Creative Commons [Attribution-NonCommercial-NoDerivatives 4.0 International] license.https://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Original article
Dong, Qian
Yu, Jian
Ding, Yan
Ji, Qing-Wei
Zhu, Rui-Rui
Wei, Yu-Zhen
Xu, Wen-Bing
Zhong, Yu-Cheng
Zhu, Zheng-Feng
Meng, Kai
Peng, Yu-Dong
Sun, Hai-Tao
Wang, Yue
Pan, Cheng-Liang
Zeng, Qiu-Tang
Yu, Kun-Wu
Phosphorylcholine-Primed Dendritic Cells Aggravate the Development of Atherosclerosis in ApoE(−/−) Mice
title Phosphorylcholine-Primed Dendritic Cells Aggravate the Development of Atherosclerosis in ApoE(−/−) Mice
title_full Phosphorylcholine-Primed Dendritic Cells Aggravate the Development of Atherosclerosis in ApoE(−/−) Mice
title_fullStr Phosphorylcholine-Primed Dendritic Cells Aggravate the Development of Atherosclerosis in ApoE(−/−) Mice
title_full_unstemmed Phosphorylcholine-Primed Dendritic Cells Aggravate the Development of Atherosclerosis in ApoE(−/−) Mice
title_short Phosphorylcholine-Primed Dendritic Cells Aggravate the Development of Atherosclerosis in ApoE(−/−) Mice
title_sort phosphorylcholine-primed dendritic cells aggravate the development of atherosclerosis in apoe(−/−) mice
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939956/
https://www.ncbi.nlm.nih.gov/pubmed/33693294
http://dx.doi.org/10.1253/circrep.CR-20-0118
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