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Clec7a expression in inflammatory macrophages orchestrates progression of acute kidney injury

Acute kidney injury (AKI) is associated with high risk of mortality, post-disease renal fibrosis, kidney dysfunction and renal failure. Renal macrophages play a key role in the pathogenesis (M1 subpopulation), healing and remodeling (M2 subpopulation) in AKI and, thus, have been a promising target f...

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Autores principales: Wang, Yaqiong, Li, Xianzhe, Xu, Xialian, Yu, Jinbo, Chen, Xiaohong, Cao, Xuesen, Zou, Jianzhou, Shen, Bo, Ding, Xiaoqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9520532/
https://www.ncbi.nlm.nih.gov/pubmed/36189317
http://dx.doi.org/10.3389/fimmu.2022.1008727
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author Wang, Yaqiong
Li, Xianzhe
Xu, Xialian
Yu, Jinbo
Chen, Xiaohong
Cao, Xuesen
Zou, Jianzhou
Shen, Bo
Ding, Xiaoqiang
author_facet Wang, Yaqiong
Li, Xianzhe
Xu, Xialian
Yu, Jinbo
Chen, Xiaohong
Cao, Xuesen
Zou, Jianzhou
Shen, Bo
Ding, Xiaoqiang
author_sort Wang, Yaqiong
collection PubMed
description Acute kidney injury (AKI) is associated with high risk of mortality, post-disease renal fibrosis, kidney dysfunction and renal failure. Renal macrophages play a key role in the pathogenesis (M1 subpopulation), healing and remodeling (M2 subpopulation) in AKI and, thus, have been a promising target for clinical treatment of AKI. Here, in a mouse renal ischemia/reperfusion injury (IRI) model for AKI, we showed that renal macrophages could be further classified into Clec7a+ M1 macrophages, Clec7a- M1 macrophages, Clec7a+ M2 macrophages and Clec7a- M2 macrophages, representing distinct macrophage populations with different functionality. Interestingly, Clec7a+ M1 macrophages exhibited potent pro-inflammatory and phagocytic effects compared to Clec7a- M1 macrophages, while Clec7a- M2 macrophages exhibited better proliferating and migrating potential, which is critical for their role in tissue repairing after injury. These data from mice were further strengthened by bioinformatics analyses using published database. In vivo, combined expression of Clec7a in M1 macrophages and depletion of Clec7a in M2 macrophages significantly improved the renal function after IRI-AKI. Together, our data suggest that Clec7a is crucial for the fine regulation of macrophage phenotype during AKI and could be a novel target for boosting clinical therapy.
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spelling pubmed-95205322022-09-30 Clec7a expression in inflammatory macrophages orchestrates progression of acute kidney injury Wang, Yaqiong Li, Xianzhe Xu, Xialian Yu, Jinbo Chen, Xiaohong Cao, Xuesen Zou, Jianzhou Shen, Bo Ding, Xiaoqiang Front Immunol Immunology Acute kidney injury (AKI) is associated with high risk of mortality, post-disease renal fibrosis, kidney dysfunction and renal failure. Renal macrophages play a key role in the pathogenesis (M1 subpopulation), healing and remodeling (M2 subpopulation) in AKI and, thus, have been a promising target for clinical treatment of AKI. Here, in a mouse renal ischemia/reperfusion injury (IRI) model for AKI, we showed that renal macrophages could be further classified into Clec7a+ M1 macrophages, Clec7a- M1 macrophages, Clec7a+ M2 macrophages and Clec7a- M2 macrophages, representing distinct macrophage populations with different functionality. Interestingly, Clec7a+ M1 macrophages exhibited potent pro-inflammatory and phagocytic effects compared to Clec7a- M1 macrophages, while Clec7a- M2 macrophages exhibited better proliferating and migrating potential, which is critical for their role in tissue repairing after injury. These data from mice were further strengthened by bioinformatics analyses using published database. In vivo, combined expression of Clec7a in M1 macrophages and depletion of Clec7a in M2 macrophages significantly improved the renal function after IRI-AKI. Together, our data suggest that Clec7a is crucial for the fine regulation of macrophage phenotype during AKI and could be a novel target for boosting clinical therapy. Frontiers Media S.A. 2022-09-15 /pmc/articles/PMC9520532/ /pubmed/36189317 http://dx.doi.org/10.3389/fimmu.2022.1008727 Text en Copyright © 2022 Wang, Li, Xu, Yu, Chen, Cao, Zou, Shen and Ding 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
Wang, Yaqiong
Li, Xianzhe
Xu, Xialian
Yu, Jinbo
Chen, Xiaohong
Cao, Xuesen
Zou, Jianzhou
Shen, Bo
Ding, Xiaoqiang
Clec7a expression in inflammatory macrophages orchestrates progression of acute kidney injury
title Clec7a expression in inflammatory macrophages orchestrates progression of acute kidney injury
title_full Clec7a expression in inflammatory macrophages orchestrates progression of acute kidney injury
title_fullStr Clec7a expression in inflammatory macrophages orchestrates progression of acute kidney injury
title_full_unstemmed Clec7a expression in inflammatory macrophages orchestrates progression of acute kidney injury
title_short Clec7a expression in inflammatory macrophages orchestrates progression of acute kidney injury
title_sort clec7a expression in inflammatory macrophages orchestrates progression of acute kidney injury
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9520532/
https://www.ncbi.nlm.nih.gov/pubmed/36189317
http://dx.doi.org/10.3389/fimmu.2022.1008727
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