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Mesenchymal stem cell transplantation alleviated atherosclerosis in systemic lupus erythematosus through reducing MDSCs

OBJECTIVE: The mechanism by which mesenchymal stem cell (MSC) transplantation alleviates atherosclerosis in systemic lupus erythematosus (SLE) remains elusive. In this study, we aim to explore the efficacy and mechanism of MSC in ameliorating atherosclerosis in SLE. METHODS: ApoE(−/−) and Fas(−/−) m...

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Autores principales: Yao, Genhong, Qi, Jingjing, Li, Xiaojing, Tang, Xiaojun, Li, Wenchao, Chen, Weiwei, Xia, Nan, Wang, Shiying, Sun, Lingyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290280/
https://www.ncbi.nlm.nih.gov/pubmed/35850768
http://dx.doi.org/10.1186/s13287-022-03002-y
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author Yao, Genhong
Qi, Jingjing
Li, Xiaojing
Tang, Xiaojun
Li, Wenchao
Chen, Weiwei
Xia, Nan
Wang, Shiying
Sun, Lingyun
author_facet Yao, Genhong
Qi, Jingjing
Li, Xiaojing
Tang, Xiaojun
Li, Wenchao
Chen, Weiwei
Xia, Nan
Wang, Shiying
Sun, Lingyun
author_sort Yao, Genhong
collection PubMed
description OBJECTIVE: The mechanism by which mesenchymal stem cell (MSC) transplantation alleviates atherosclerosis in systemic lupus erythematosus (SLE) remains elusive. In this study, we aim to explore the efficacy and mechanism of MSC in ameliorating atherosclerosis in SLE. METHODS: ApoE(−/−) and Fas(−/−) mice on the B6 background were cross-bred to generate SLE mice with atherosclerosis. Myeloid-derived suppressor cells (MDSCs) were sorted and quantified. The apoE(−/−)Fas(−/−) mice were either treated with anti-Gr antibody or injected with MDSCs. The lupus-like autoimmunity and atherosclerotic lesions were evaluated. Furthermore, the apoE(−/−)Fas(−/−) mice were transplanted with MSCs and lupus-like autoimmunity and atherosclerotic lesions were assessed. RESULTS: MDSCs in peripheral blood, spleen, draining lymph nodes increased in apoE(−/−)Fas(−/−) mice compared with B6 mice. Moreover, the adoptive transfer of MDSCs aggravated both atherosclerosis and SLE pathologies, whereas depleting MDSCs ameliorated those pathologies in apoE(−/−)Fas(−/−) mice. MSC transplantation in apoE(−/−)Fas(−/−) mice decreased the percentage of MDSCs, alleviated the typical atherosclerotic lesions, including atherosclerotic lesions in aortae and liver, and reduced serum cholesterol, triglyceride and low-density lipoprotein levels. MSC transplantation also reduced SLE pathologies, including splenomegaly, glomerular lesions, anti-dsDNA antibody in serum, urine protein and serum creatinine. Moreover, MSC transplantation regulated the generation and function of MDSCs through secreting prostaglandin E 2 (PGE2). CONCLUSION: Taken together, these results indicated that the increased MDSCs contributed to atherosclerosis in SLE. MSC transplantation ameliorated the atherosclerosis and SLE through reducing MDSCs by secreting PGE2. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-022-03002-y.
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spelling pubmed-92902802022-07-19 Mesenchymal stem cell transplantation alleviated atherosclerosis in systemic lupus erythematosus through reducing MDSCs Yao, Genhong Qi, Jingjing Li, Xiaojing Tang, Xiaojun Li, Wenchao Chen, Weiwei Xia, Nan Wang, Shiying Sun, Lingyun Stem Cell Res Ther Research OBJECTIVE: The mechanism by which mesenchymal stem cell (MSC) transplantation alleviates atherosclerosis in systemic lupus erythematosus (SLE) remains elusive. In this study, we aim to explore the efficacy and mechanism of MSC in ameliorating atherosclerosis in SLE. METHODS: ApoE(−/−) and Fas(−/−) mice on the B6 background were cross-bred to generate SLE mice with atherosclerosis. Myeloid-derived suppressor cells (MDSCs) were sorted and quantified. The apoE(−/−)Fas(−/−) mice were either treated with anti-Gr antibody or injected with MDSCs. The lupus-like autoimmunity and atherosclerotic lesions were evaluated. Furthermore, the apoE(−/−)Fas(−/−) mice were transplanted with MSCs and lupus-like autoimmunity and atherosclerotic lesions were assessed. RESULTS: MDSCs in peripheral blood, spleen, draining lymph nodes increased in apoE(−/−)Fas(−/−) mice compared with B6 mice. Moreover, the adoptive transfer of MDSCs aggravated both atherosclerosis and SLE pathologies, whereas depleting MDSCs ameliorated those pathologies in apoE(−/−)Fas(−/−) mice. MSC transplantation in apoE(−/−)Fas(−/−) mice decreased the percentage of MDSCs, alleviated the typical atherosclerotic lesions, including atherosclerotic lesions in aortae and liver, and reduced serum cholesterol, triglyceride and low-density lipoprotein levels. MSC transplantation also reduced SLE pathologies, including splenomegaly, glomerular lesions, anti-dsDNA antibody in serum, urine protein and serum creatinine. Moreover, MSC transplantation regulated the generation and function of MDSCs through secreting prostaglandin E 2 (PGE2). CONCLUSION: Taken together, these results indicated that the increased MDSCs contributed to atherosclerosis in SLE. MSC transplantation ameliorated the atherosclerosis and SLE through reducing MDSCs by secreting PGE2. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-022-03002-y. BioMed Central 2022-07-18 /pmc/articles/PMC9290280/ /pubmed/35850768 http://dx.doi.org/10.1186/s13287-022-03002-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yao, Genhong
Qi, Jingjing
Li, Xiaojing
Tang, Xiaojun
Li, Wenchao
Chen, Weiwei
Xia, Nan
Wang, Shiying
Sun, Lingyun
Mesenchymal stem cell transplantation alleviated atherosclerosis in systemic lupus erythematosus through reducing MDSCs
title Mesenchymal stem cell transplantation alleviated atherosclerosis in systemic lupus erythematosus through reducing MDSCs
title_full Mesenchymal stem cell transplantation alleviated atherosclerosis in systemic lupus erythematosus through reducing MDSCs
title_fullStr Mesenchymal stem cell transplantation alleviated atherosclerosis in systemic lupus erythematosus through reducing MDSCs
title_full_unstemmed Mesenchymal stem cell transplantation alleviated atherosclerosis in systemic lupus erythematosus through reducing MDSCs
title_short Mesenchymal stem cell transplantation alleviated atherosclerosis in systemic lupus erythematosus through reducing MDSCs
title_sort mesenchymal stem cell transplantation alleviated atherosclerosis in systemic lupus erythematosus through reducing mdscs
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290280/
https://www.ncbi.nlm.nih.gov/pubmed/35850768
http://dx.doi.org/10.1186/s13287-022-03002-y
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