Macrophage Polarization Modulates Development of Systemic Lupus Erythematosus

Background/Aims: Macrophages have recently been shown to play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). However, the underlying mechanisms remain unclear. Methods: Here, we used an activated lymphocyte-derived DNA (ALD-DNA) method to induce SLE in mice. We used a mac...

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Main Authors: Feng Li, Yongsheng Yang, Xiaohua Zhu, Lan Huang, Jinhua Xu
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2015-10-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:http://www.karger.com/Article/FullText/430251
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author Feng Li
Yongsheng Yang
Xiaohua Zhu
Lan Huang
Jinhua Xu
author_facet Feng Li
Yongsheng Yang
Xiaohua Zhu
Lan Huang
Jinhua Xu
author_sort Feng Li
collection DOAJ
description Background/Aims: Macrophages have recently been shown to play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). However, the underlying mechanisms remain unclear. Methods: Here, we used an activated lymphocyte-derived DNA (ALD-DNA) method to induce SLE in mice. We used a macrophage-specific eliminator clodronate to selectively deplete macrophages in mice. We isolated macrophages from bone marrow of the mice and used cytokines to differentiate M1 and M2 macrophages, respectively. Adoptive transplantation of M1 or M2 macrophages was performed in clodronate-treated mice. The effects on SLE were evaluated by serum anti-dsDNA autoantibody, by renal pathological changes, and by urine protein levels. Results: ALD-DNA induced SLE-like features in mice, manifested by induction of serum anti-dsDNA autoantibody, by renal pathological changes, and by increases in urine protein levels. Clodronate significantly decreased macrophages in mice, which significantly increased SLE severity. Adoptive transplantation of M2, but not M1 macrophages significantly reduced SLE severity in clodronate- and ALD-DNA-treated mice. Conclusion: M1 and M2 macrophages play different roles in development of SLE. M1 macrophages increase the severity of SLE, while M2 macrophages reduce it. Modulation of macrophage polarity may be an attractive therapy for SLE.
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spelling doaj.art-64f6ebe6e5fa48dc8bbb58cea117df972022-12-21T18:39:34ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-10-013741279128810.1159/000430251430251Macrophage Polarization Modulates Development of Systemic Lupus ErythematosusFeng LiYongsheng YangXiaohua ZhuLan HuangJinhua XuBackground/Aims: Macrophages have recently been shown to play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). However, the underlying mechanisms remain unclear. Methods: Here, we used an activated lymphocyte-derived DNA (ALD-DNA) method to induce SLE in mice. We used a macrophage-specific eliminator clodronate to selectively deplete macrophages in mice. We isolated macrophages from bone marrow of the mice and used cytokines to differentiate M1 and M2 macrophages, respectively. Adoptive transplantation of M1 or M2 macrophages was performed in clodronate-treated mice. The effects on SLE were evaluated by serum anti-dsDNA autoantibody, by renal pathological changes, and by urine protein levels. Results: ALD-DNA induced SLE-like features in mice, manifested by induction of serum anti-dsDNA autoantibody, by renal pathological changes, and by increases in urine protein levels. Clodronate significantly decreased macrophages in mice, which significantly increased SLE severity. Adoptive transplantation of M2, but not M1 macrophages significantly reduced SLE severity in clodronate- and ALD-DNA-treated mice. Conclusion: M1 and M2 macrophages play different roles in development of SLE. M1 macrophages increase the severity of SLE, while M2 macrophages reduce it. Modulation of macrophage polarity may be an attractive therapy for SLE.http://www.karger.com/Article/FullText/430251Systemic lupus erythematosus (SLE)Macrophage polarizationM1 macrophageM2 macrophageClodronateALD-DNAAdoptive transplantation
spellingShingle Feng Li
Yongsheng Yang
Xiaohua Zhu
Lan Huang
Jinhua Xu
Macrophage Polarization Modulates Development of Systemic Lupus Erythematosus
Cellular Physiology and Biochemistry
Systemic lupus erythematosus (SLE)
Macrophage polarization
M1 macrophage
M2 macrophage
Clodronate
ALD-DNA
Adoptive transplantation
title Macrophage Polarization Modulates Development of Systemic Lupus Erythematosus
title_full Macrophage Polarization Modulates Development of Systemic Lupus Erythematosus
title_fullStr Macrophage Polarization Modulates Development of Systemic Lupus Erythematosus
title_full_unstemmed Macrophage Polarization Modulates Development of Systemic Lupus Erythematosus
title_short Macrophage Polarization Modulates Development of Systemic Lupus Erythematosus
title_sort macrophage polarization modulates development of systemic lupus erythematosus
topic Systemic lupus erythematosus (SLE)
Macrophage polarization
M1 macrophage
M2 macrophage
Clodronate
ALD-DNA
Adoptive transplantation
url http://www.karger.com/Article/FullText/430251
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