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TGF-β-Induced CD8(+)CD103(+) Regulatory T Cells Show Potent Therapeutic Effect on Chronic Graft-versus-Host Disease Lupus by Suppressing B Cells
Lupus nephritis is one of most severe complications of systemic erythematosus lupus and current approaches are not curative for lupus nephritis. Although CD4(+)Foxp3(+) regulatory T cells (Treg) are crucial for prevention of autoimmunity, the therapeutic effect of these cells on lupus nephritis is n...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797539/ https://www.ncbi.nlm.nih.gov/pubmed/29441062 http://dx.doi.org/10.3389/fimmu.2018.00035 |
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author | Zhong, Haowen Liu, Ya Xu, Zhenjian Liang, Peifeng Yang, Hui Zhang, Xiao Zhao, Jun Chen, Junzhen Fu, Sha Tang, Ying Lv, Jun Wang, Julie Olsen, Nancy Xu, Anping Zheng, Song Guo |
author_facet | Zhong, Haowen Liu, Ya Xu, Zhenjian Liang, Peifeng Yang, Hui Zhang, Xiao Zhao, Jun Chen, Junzhen Fu, Sha Tang, Ying Lv, Jun Wang, Julie Olsen, Nancy Xu, Anping Zheng, Song Guo |
author_sort | Zhong, Haowen |
collection | PubMed |
description | Lupus nephritis is one of most severe complications of systemic erythematosus lupus and current approaches are not curative for lupus nephritis. Although CD4(+)Foxp3(+) regulatory T cells (Treg) are crucial for prevention of autoimmunity, the therapeutic effect of these cells on lupus nephritis is not satisfactory. We previously reported that CD8(+)CD103(+) Treg induced ex vivo with TGF-β1 and IL-2 (CD8(+)CD103(+) iTreg), regardless of Foxp3 expression, displayed potent immunosuppressive effect on Th cell response and had therapeutic effect on Th cell-mediated colitis. Here, we tested whether CD8(+)CD103(+) iTreg can ameliorate lupus nephritis and determined potential molecular mechanisms. Adoptive transfer of CD8(+)CD103(+) iTreg but not control cells to chronic graft-versus-host disease with a typical lupus syndrome showed decreased levels of autoantibodies and proteinuria, reduced renal pathological lesions, lowered renal deposition of IgG/C3, and improved survival. CD8(+)CD103(+) iTreg cells suppressed not only T helper cells but also B cell responses directly that may involve in both TGF-β and IL-10 signals. Using RNA-seq, we demonstrated CD8(+)CD103(+) iTreg have its own unique expression profiles of transcription factors. Thus, current study has identified and extended the target cells of CD8(+)CD103(+) iTreg and provided a possible application of this new iTreg subset on lupus nephritis and other autoimmune diseases. |
format | Online Article Text |
id | pubmed-5797539 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-57975392018-02-13 TGF-β-Induced CD8(+)CD103(+) Regulatory T Cells Show Potent Therapeutic Effect on Chronic Graft-versus-Host Disease Lupus by Suppressing B Cells Zhong, Haowen Liu, Ya Xu, Zhenjian Liang, Peifeng Yang, Hui Zhang, Xiao Zhao, Jun Chen, Junzhen Fu, Sha Tang, Ying Lv, Jun Wang, Julie Olsen, Nancy Xu, Anping Zheng, Song Guo Front Immunol Immunology Lupus nephritis is one of most severe complications of systemic erythematosus lupus and current approaches are not curative for lupus nephritis. Although CD4(+)Foxp3(+) regulatory T cells (Treg) are crucial for prevention of autoimmunity, the therapeutic effect of these cells on lupus nephritis is not satisfactory. We previously reported that CD8(+)CD103(+) Treg induced ex vivo with TGF-β1 and IL-2 (CD8(+)CD103(+) iTreg), regardless of Foxp3 expression, displayed potent immunosuppressive effect on Th cell response and had therapeutic effect on Th cell-mediated colitis. Here, we tested whether CD8(+)CD103(+) iTreg can ameliorate lupus nephritis and determined potential molecular mechanisms. Adoptive transfer of CD8(+)CD103(+) iTreg but not control cells to chronic graft-versus-host disease with a typical lupus syndrome showed decreased levels of autoantibodies and proteinuria, reduced renal pathological lesions, lowered renal deposition of IgG/C3, and improved survival. CD8(+)CD103(+) iTreg cells suppressed not only T helper cells but also B cell responses directly that may involve in both TGF-β and IL-10 signals. Using RNA-seq, we demonstrated CD8(+)CD103(+) iTreg have its own unique expression profiles of transcription factors. Thus, current study has identified and extended the target cells of CD8(+)CD103(+) iTreg and provided a possible application of this new iTreg subset on lupus nephritis and other autoimmune diseases. Frontiers Media S.A. 2018-01-30 /pmc/articles/PMC5797539/ /pubmed/29441062 http://dx.doi.org/10.3389/fimmu.2018.00035 Text en Copyright © 2018 Zhong, Liu, Xu, Liang, Yang, Zhang, Zhao, Chen, Fu, Tang, Lv, Wang, Olsen, Xu and Zheng. http://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 Zhong, Haowen Liu, Ya Xu, Zhenjian Liang, Peifeng Yang, Hui Zhang, Xiao Zhao, Jun Chen, Junzhen Fu, Sha Tang, Ying Lv, Jun Wang, Julie Olsen, Nancy Xu, Anping Zheng, Song Guo TGF-β-Induced CD8(+)CD103(+) Regulatory T Cells Show Potent Therapeutic Effect on Chronic Graft-versus-Host Disease Lupus by Suppressing B Cells |
title | TGF-β-Induced CD8(+)CD103(+) Regulatory T Cells Show Potent Therapeutic Effect on Chronic Graft-versus-Host Disease Lupus by Suppressing B Cells |
title_full | TGF-β-Induced CD8(+)CD103(+) Regulatory T Cells Show Potent Therapeutic Effect on Chronic Graft-versus-Host Disease Lupus by Suppressing B Cells |
title_fullStr | TGF-β-Induced CD8(+)CD103(+) Regulatory T Cells Show Potent Therapeutic Effect on Chronic Graft-versus-Host Disease Lupus by Suppressing B Cells |
title_full_unstemmed | TGF-β-Induced CD8(+)CD103(+) Regulatory T Cells Show Potent Therapeutic Effect on Chronic Graft-versus-Host Disease Lupus by Suppressing B Cells |
title_short | TGF-β-Induced CD8(+)CD103(+) Regulatory T Cells Show Potent Therapeutic Effect on Chronic Graft-versus-Host Disease Lupus by Suppressing B Cells |
title_sort | tgf-β-induced cd8(+)cd103(+) regulatory t cells show potent therapeutic effect on chronic graft-versus-host disease lupus by suppressing b cells |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797539/ https://www.ncbi.nlm.nih.gov/pubmed/29441062 http://dx.doi.org/10.3389/fimmu.2018.00035 |
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