The role of regulatory B cells (Bregs) in the Tregs-amplifying effect of Sirolimus

Sirolimus can significantly amplify regulatory T cells (Tregs) in vivo and in vitro, but the specific mechanism of this has not been well documented. The role of regulatory B cells (Bregs) in the Tregs-amplifying effect of Sirolimus was investigated in peripheral blood mononuclear cells (PBMCs) in v...

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Veröffentlicht in:International immunopharmacology 2016-09, Vol.38, p.90-96
Hauptverfasser: Song, Jiyong, Xiao, Li, Du, Guosheng, Gao, Yu, Chen, Wen, Yang, Shaozhen, Fan, Wenmei, Shi, Bingyi
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container_issue
container_start_page 90
container_title International immunopharmacology
container_volume 38
creator Song, Jiyong
Xiao, Li
Du, Guosheng
Gao, Yu
Chen, Wen
Yang, Shaozhen
Fan, Wenmei
Shi, Bingyi
description Sirolimus can significantly amplify regulatory T cells (Tregs) in vivo and in vitro, but the specific mechanism of this has not been well documented. The role of regulatory B cells (Bregs) in the Tregs-amplifying effect of Sirolimus was investigated in peripheral blood mononuclear cells (PBMCs) in vitro in this study. The results showed that the percentages of both CD19+CD24+CD38+TGF-β1+ Bregs and CD19+CD24+CD38+IL-10+ Bregs to B cells were elevated by Sirolimus in PBMCs including B cells. Sirolimus significantly enhances the cytokine production of transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) in PBMCs with B cells, and the enhancement significantly decreased in PBMCs without B cells. The percentage of CD4+CD25+Foxp3+ Tregs to T cells was also elevated by Sirolimus in PBMCs including B cells. The elevation of Tregs percentage decreased in PBMCs without B cells and recovered when additional TGF-β1 and IL-10 were added. The amplification of Tregs by Sirolimus was partially inhibited when either TGF-β1 or IL-10 was neutralized, and it even disappeared when these two cytokines were both neutralized. These results indicate that Sirolimus can amplify Bregs and Tregs in PBMCs in vitro, and Bregs may be the why Sirolimus amplifies Tregs. •It is the first study on Sirolimus amplifying Breg in vitro.•The role of B cells in Sirolimus amplifying Treg was intensively investigated.•A hypothesis that Breg is one link of Sirolimus amplifying Treg was suggested.
doi_str_mv 10.1016/j.intimp.2016.05.014
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The role of regulatory B cells (Bregs) in the Tregs-amplifying effect of Sirolimus was investigated in peripheral blood mononuclear cells (PBMCs) in vitro in this study. The results showed that the percentages of both CD19+CD24+CD38+TGF-β1+ Bregs and CD19+CD24+CD38+IL-10+ Bregs to B cells were elevated by Sirolimus in PBMCs including B cells. Sirolimus significantly enhances the cytokine production of transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) in PBMCs with B cells, and the enhancement significantly decreased in PBMCs without B cells. The percentage of CD4+CD25+Foxp3+ Tregs to T cells was also elevated by Sirolimus in PBMCs including B cells. The elevation of Tregs percentage decreased in PBMCs without B cells and recovered when additional TGF-β1 and IL-10 were added. The amplification of Tregs by Sirolimus was partially inhibited when either TGF-β1 or IL-10 was neutralized, and it even disappeared when these two cytokines were both neutralized. These results indicate that Sirolimus can amplify Bregs and Tregs in PBMCs in vitro, and Bregs may be the why Sirolimus amplifies Tregs. •It is the first study on Sirolimus amplifying Breg in vitro.•The role of B cells in Sirolimus amplifying Treg was intensively investigated.•A hypothesis that Breg is one link of Sirolimus amplifying Treg was suggested.</description><identifier>ISSN: 1567-5769</identifier><identifier>EISSN: 1878-1705</identifier><identifier>DOI: 10.1016/j.intimp.2016.05.014</identifier><identifier>PMID: 27258186</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>B-Lymphocytes, Regulatory - drug effects ; B-Lymphocytes, Regulatory - immunology ; Breg ; Cell Communication ; Cells, Cultured ; Forkhead Transcription Factors - metabolism ; Humans ; Immunosuppressive agent ; Immunosuppressive Agents - pharmacology ; Interleukin-10 - metabolism ; Leukocytes, Mononuclear - drug effects ; Leukocytes, Mononuclear - immunology ; Lymphocyte Activation - drug effects ; Lymphocyte subset ; Organ transplantation ; Sirolimus ; Sirolimus - pharmacology ; T-Lymphocytes, Regulatory - drug effects ; T-Lymphocytes, Regulatory - immunology ; Transforming Growth Factor beta1 - metabolism ; Treg</subject><ispartof>International immunopharmacology, 2016-09, Vol.38, p.90-96</ispartof><rights>2016</rights><rights>Copyright © 2016. 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These results indicate that Sirolimus can amplify Bregs and Tregs in PBMCs in vitro, and Bregs may be the why Sirolimus amplifies Tregs. •It is the first study on Sirolimus amplifying Breg in vitro.•The role of B cells in Sirolimus amplifying Treg was intensively investigated.•A hypothesis that Breg is one link of Sirolimus amplifying Treg was suggested.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>27258186</pmid><doi>10.1016/j.intimp.2016.05.014</doi><tpages>7</tpages></addata></record>
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subjects B-Lymphocytes, Regulatory - drug effects
B-Lymphocytes, Regulatory - immunology
Breg
Cell Communication
Cells, Cultured
Forkhead Transcription Factors - metabolism
Humans
Immunosuppressive agent
Immunosuppressive Agents - pharmacology
Interleukin-10 - metabolism
Leukocytes, Mononuclear - drug effects
Leukocytes, Mononuclear - immunology
Lymphocyte Activation - drug effects
Lymphocyte subset
Organ transplantation
Sirolimus
Sirolimus - pharmacology
T-Lymphocytes, Regulatory - drug effects
T-Lymphocytes, Regulatory - immunology
Transforming Growth Factor beta1 - metabolism
Treg
title The role of regulatory B cells (Bregs) in the Tregs-amplifying effect of Sirolimus
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