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Myeloid-Derived Suppressor Cells Induce Podocyte Injury Through Increasing Reactive Oxygen Species in Lupus Nephritis

The expansion of myeloid-derived suppressor cells (MDSCs) has been documented in murine models and patients with lupus nephritis (LN), but the exact role of MDSCs in this process remains largely unknown. In this study, we investigated whether MDSCs are involved in the process of podocyte injury in t...

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Autores principales: Zhang, Dongya, Xu, Jingjing, Ren, Jing, Ding, Liang, Shi, Guoping, Li, Dan, Dou, Huan, Hou, Yayi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026681/
https://www.ncbi.nlm.nih.gov/pubmed/29988544
http://dx.doi.org/10.3389/fimmu.2018.01443
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author Zhang, Dongya
Xu, Jingjing
Ren, Jing
Ding, Liang
Shi, Guoping
Li, Dan
Dou, Huan
Hou, Yayi
author_facet Zhang, Dongya
Xu, Jingjing
Ren, Jing
Ding, Liang
Shi, Guoping
Li, Dan
Dou, Huan
Hou, Yayi
author_sort Zhang, Dongya
collection PubMed
description The expansion of myeloid-derived suppressor cells (MDSCs) has been documented in murine models and patients with lupus nephritis (LN), but the exact role of MDSCs in this process remains largely unknown. In this study, we investigated whether MDSCs are involved in the process of podocyte injury in the development of LN. In toll-like receptor-7 (TLR-7) agonist imiquimod-induced lupus mice, we found the severe podocyte injury in glomeruli of lupus mice and significant expansion of MDSCs in spleens and kidneys of lupus mice. The function of TLR-7 activated MDSCs was enhanced including the increased generation of reactive oxygen species (ROS) in vivo and in vitro. Moreover, the ROS production of MDSCs induced podocyte injury through activating the p-38MAPK and NF-kB signaling. Furthermore, we verified that podocyte injury was indeed correlated with expansion of MDSCs and their ROS secretion in LN of pristane-induced lupus mice. These findings first indicate that the podocyte injury in LN was associated with the increased MDSCs in kidney and MDSCs may be a promising therapeutic target of LN in the future.
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spelling pubmed-60266812018-07-09 Myeloid-Derived Suppressor Cells Induce Podocyte Injury Through Increasing Reactive Oxygen Species in Lupus Nephritis Zhang, Dongya Xu, Jingjing Ren, Jing Ding, Liang Shi, Guoping Li, Dan Dou, Huan Hou, Yayi Front Immunol Immunology The expansion of myeloid-derived suppressor cells (MDSCs) has been documented in murine models and patients with lupus nephritis (LN), but the exact role of MDSCs in this process remains largely unknown. In this study, we investigated whether MDSCs are involved in the process of podocyte injury in the development of LN. In toll-like receptor-7 (TLR-7) agonist imiquimod-induced lupus mice, we found the severe podocyte injury in glomeruli of lupus mice and significant expansion of MDSCs in spleens and kidneys of lupus mice. The function of TLR-7 activated MDSCs was enhanced including the increased generation of reactive oxygen species (ROS) in vivo and in vitro. Moreover, the ROS production of MDSCs induced podocyte injury through activating the p-38MAPK and NF-kB signaling. Furthermore, we verified that podocyte injury was indeed correlated with expansion of MDSCs and their ROS secretion in LN of pristane-induced lupus mice. These findings first indicate that the podocyte injury in LN was associated with the increased MDSCs in kidney and MDSCs may be a promising therapeutic target of LN in the future. Frontiers Media S.A. 2018-06-25 /pmc/articles/PMC6026681/ /pubmed/29988544 http://dx.doi.org/10.3389/fimmu.2018.01443 Text en Copyright © 2018 Zhang, Xu, Ren, Ding, Shi, Li, Dou and Hou. 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 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
Zhang, Dongya
Xu, Jingjing
Ren, Jing
Ding, Liang
Shi, Guoping
Li, Dan
Dou, Huan
Hou, Yayi
Myeloid-Derived Suppressor Cells Induce Podocyte Injury Through Increasing Reactive Oxygen Species in Lupus Nephritis
title Myeloid-Derived Suppressor Cells Induce Podocyte Injury Through Increasing Reactive Oxygen Species in Lupus Nephritis
title_full Myeloid-Derived Suppressor Cells Induce Podocyte Injury Through Increasing Reactive Oxygen Species in Lupus Nephritis
title_fullStr Myeloid-Derived Suppressor Cells Induce Podocyte Injury Through Increasing Reactive Oxygen Species in Lupus Nephritis
title_full_unstemmed Myeloid-Derived Suppressor Cells Induce Podocyte Injury Through Increasing Reactive Oxygen Species in Lupus Nephritis
title_short Myeloid-Derived Suppressor Cells Induce Podocyte Injury Through Increasing Reactive Oxygen Species in Lupus Nephritis
title_sort myeloid-derived suppressor cells induce podocyte injury through increasing reactive oxygen species in lupus nephritis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026681/
https://www.ncbi.nlm.nih.gov/pubmed/29988544
http://dx.doi.org/10.3389/fimmu.2018.01443
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