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Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion
Immature or semi-mature dendritic cells (DCs) represent tolerogenic maturation stages that can convert naive T cells into Foxp3(+) induced regulatory T cells (iTreg). Here we found that murine bone marrow-derived DCs (BM-DCs) treated with cholera toxin (CT) matured by up-regulating MHC-II and costim...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536293/ https://www.ncbi.nlm.nih.gov/pubmed/28759565 http://dx.doi.org/10.1371/journal.pone.0178114 |
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author | Silva-Vilches, Cinthia Pletinckx, Katrien Lohnert, Miriam Pavlovic, Vladimir Ashour, Diyaaeldin John, Vini Vendelova, Emilia Kneitz, Susanne Zhou, Jie Chen, Rena Reinheckel, Thomas Mueller, Thomas D. Bodem, Jochen Lutz, Manfred B. |
author_facet | Silva-Vilches, Cinthia Pletinckx, Katrien Lohnert, Miriam Pavlovic, Vladimir Ashour, Diyaaeldin John, Vini Vendelova, Emilia Kneitz, Susanne Zhou, Jie Chen, Rena Reinheckel, Thomas Mueller, Thomas D. Bodem, Jochen Lutz, Manfred B. |
author_sort | Silva-Vilches, Cinthia |
collection | PubMed |
description | Immature or semi-mature dendritic cells (DCs) represent tolerogenic maturation stages that can convert naive T cells into Foxp3(+) induced regulatory T cells (iTreg). Here we found that murine bone marrow-derived DCs (BM-DCs) treated with cholera toxin (CT) matured by up-regulating MHC-II and costimulatory molecules using either high or low doses of CT (CT(hi), CT(lo)) or with cAMP, a known mediator CT signals. However, all three conditions also induced mRNA of both isoforms of the tolerogenic molecule cytotoxic T lymphocyte antigen 2 (CTLA-2α and CTLA-2β). Only DCs matured under CT(hi) conditions secreted IL-1β, IL-6 and IL-23 leading to the instruction of Th17 cell polarization. In contrast, CT(lo)- or cAMP-DCs resembled semi-mature DCs and enhanced TGF-β-dependent Foxp3(+) iTreg conversion. iTreg conversion could be reduced using siRNA blocking of CTLA-2 and reversely, addition of recombinant CTLA-2α increased iTreg conversion in vitro. Injection of CT(lo)- or cAMP-DCs exerted MOG peptide-specific protective effects in experimental autoimmune encephalomyelitis (EAE) by inducing Foxp3(+) Tregs and reducing Th17 responses. Together, we identified CTLA-2 production by DCs as a novel tolerogenic mediator of TGF-β-mediated iTreg induction in vitro and in vivo. The CT-induced and cAMP-mediated up-regulation of CTLA-2 also may point to a novel immune evasion mechanism of Vibrio cholerae. |
format | Online Article Text |
id | pubmed-5536293 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55362932017-08-07 Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion Silva-Vilches, Cinthia Pletinckx, Katrien Lohnert, Miriam Pavlovic, Vladimir Ashour, Diyaaeldin John, Vini Vendelova, Emilia Kneitz, Susanne Zhou, Jie Chen, Rena Reinheckel, Thomas Mueller, Thomas D. Bodem, Jochen Lutz, Manfred B. PLoS One Research Article Immature or semi-mature dendritic cells (DCs) represent tolerogenic maturation stages that can convert naive T cells into Foxp3(+) induced regulatory T cells (iTreg). Here we found that murine bone marrow-derived DCs (BM-DCs) treated with cholera toxin (CT) matured by up-regulating MHC-II and costimulatory molecules using either high or low doses of CT (CT(hi), CT(lo)) or with cAMP, a known mediator CT signals. However, all three conditions also induced mRNA of both isoforms of the tolerogenic molecule cytotoxic T lymphocyte antigen 2 (CTLA-2α and CTLA-2β). Only DCs matured under CT(hi) conditions secreted IL-1β, IL-6 and IL-23 leading to the instruction of Th17 cell polarization. In contrast, CT(lo)- or cAMP-DCs resembled semi-mature DCs and enhanced TGF-β-dependent Foxp3(+) iTreg conversion. iTreg conversion could be reduced using siRNA blocking of CTLA-2 and reversely, addition of recombinant CTLA-2α increased iTreg conversion in vitro. Injection of CT(lo)- or cAMP-DCs exerted MOG peptide-specific protective effects in experimental autoimmune encephalomyelitis (EAE) by inducing Foxp3(+) Tregs and reducing Th17 responses. Together, we identified CTLA-2 production by DCs as a novel tolerogenic mediator of TGF-β-mediated iTreg induction in vitro and in vivo. The CT-induced and cAMP-mediated up-regulation of CTLA-2 also may point to a novel immune evasion mechanism of Vibrio cholerae. Public Library of Science 2017-07-31 /pmc/articles/PMC5536293/ /pubmed/28759565 http://dx.doi.org/10.1371/journal.pone.0178114 Text en © 2017 Silva-Vilches et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Silva-Vilches, Cinthia Pletinckx, Katrien Lohnert, Miriam Pavlovic, Vladimir Ashour, Diyaaeldin John, Vini Vendelova, Emilia Kneitz, Susanne Zhou, Jie Chen, Rena Reinheckel, Thomas Mueller, Thomas D. Bodem, Jochen Lutz, Manfred B. Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion |
title | Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion |
title_full | Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion |
title_fullStr | Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion |
title_full_unstemmed | Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion |
title_short | Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion |
title_sort | low doses of cholera toxin and its mediator camp induce ctla-2 secretion by dendritic cells to enhance regulatory t cell conversion |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536293/ https://www.ncbi.nlm.nih.gov/pubmed/28759565 http://dx.doi.org/10.1371/journal.pone.0178114 |
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