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Therapeutic Use of a Selective S1P(1) Receptor Modulator Ponesimod in Autoimmune Diabetes
In the present study, we investigated the therapeutic potential of a selective S1P(1) receptor modulator, ponesimod, to protect and reverse autoimmune diabetes in non-obese diabetic (NOD) mice. Ponesimod was administered orally to NOD mice starting at 6, 10, 13 and 16 weeks of age up to 35 weeks of...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811978/ https://www.ncbi.nlm.nih.gov/pubmed/24204793 http://dx.doi.org/10.1371/journal.pone.0077296 |
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author | You, Sylvaine Piali, Luca Kuhn, Chantal Steiner, Beat Sauvaget, Virginia Valette, Fabrice Clozel, Martine Bach, Jean-François Chatenoud, Lucienne |
author_facet | You, Sylvaine Piali, Luca Kuhn, Chantal Steiner, Beat Sauvaget, Virginia Valette, Fabrice Clozel, Martine Bach, Jean-François Chatenoud, Lucienne |
author_sort | You, Sylvaine |
collection | PubMed |
description | In the present study, we investigated the therapeutic potential of a selective S1P(1) receptor modulator, ponesimod, to protect and reverse autoimmune diabetes in non-obese diabetic (NOD) mice. Ponesimod was administered orally to NOD mice starting at 6, 10, 13 and 16 weeks of age up to 35 weeks of age or to NOD mice showing recent onset diabetes. Peripheral blood and spleen B and T cell counts were significantly reduced after ponesimod administration. In pancreatic lymph nodes, B lymphocytes were increased and expressed a transitional 1-like phenotype. Chronic oral ponesimod treatment efficiently prevented autoimmune diabetes in 6, 10 and 16 week-old pre-diabetic NOD mice. Treatment withdrawal led to synchronized disease relapse. Ponesimod did not inhibit the differentiation of autoreactive T cells as assessed by adoptive transfer of lymphocytes from treated disease-free NOD mice. In addition, it did not affect the migration, proliferation and activation of transgenic BDC2.5 cells into the target tissue. However, ponesimod inhibited spreading of the T cell responses to islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). Treatment of diabetic NOD mice with ponesimod induced disease remission. However, here again, upon treatment cessation, the disease rapidly recurred. This recurrence was effectively prevented by combination treatment with a CD3 antibody leading to the restoration of self-tolerance. In conclusion, treatment with a selective S1P(1) modulator in combination with CD3 antibody represents a promising therapeutic approach for the treatment of autoimmune diabetes. |
format | Online Article Text |
id | pubmed-3811978 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38119782013-11-07 Therapeutic Use of a Selective S1P(1) Receptor Modulator Ponesimod in Autoimmune Diabetes You, Sylvaine Piali, Luca Kuhn, Chantal Steiner, Beat Sauvaget, Virginia Valette, Fabrice Clozel, Martine Bach, Jean-François Chatenoud, Lucienne PLoS One Research Article In the present study, we investigated the therapeutic potential of a selective S1P(1) receptor modulator, ponesimod, to protect and reverse autoimmune diabetes in non-obese diabetic (NOD) mice. Ponesimod was administered orally to NOD mice starting at 6, 10, 13 and 16 weeks of age up to 35 weeks of age or to NOD mice showing recent onset diabetes. Peripheral blood and spleen B and T cell counts were significantly reduced after ponesimod administration. In pancreatic lymph nodes, B lymphocytes were increased and expressed a transitional 1-like phenotype. Chronic oral ponesimod treatment efficiently prevented autoimmune diabetes in 6, 10 and 16 week-old pre-diabetic NOD mice. Treatment withdrawal led to synchronized disease relapse. Ponesimod did not inhibit the differentiation of autoreactive T cells as assessed by adoptive transfer of lymphocytes from treated disease-free NOD mice. In addition, it did not affect the migration, proliferation and activation of transgenic BDC2.5 cells into the target tissue. However, ponesimod inhibited spreading of the T cell responses to islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). Treatment of diabetic NOD mice with ponesimod induced disease remission. However, here again, upon treatment cessation, the disease rapidly recurred. This recurrence was effectively prevented by combination treatment with a CD3 antibody leading to the restoration of self-tolerance. In conclusion, treatment with a selective S1P(1) modulator in combination with CD3 antibody represents a promising therapeutic approach for the treatment of autoimmune diabetes. Public Library of Science 2013-10-24 /pmc/articles/PMC3811978/ /pubmed/24204793 http://dx.doi.org/10.1371/journal.pone.0077296 Text en © 2013 You 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article You, Sylvaine Piali, Luca Kuhn, Chantal Steiner, Beat Sauvaget, Virginia Valette, Fabrice Clozel, Martine Bach, Jean-François Chatenoud, Lucienne Therapeutic Use of a Selective S1P(1) Receptor Modulator Ponesimod in Autoimmune Diabetes |
title | Therapeutic Use of a Selective S1P(1) Receptor Modulator Ponesimod in Autoimmune Diabetes |
title_full | Therapeutic Use of a Selective S1P(1) Receptor Modulator Ponesimod in Autoimmune Diabetes |
title_fullStr | Therapeutic Use of a Selective S1P(1) Receptor Modulator Ponesimod in Autoimmune Diabetes |
title_full_unstemmed | Therapeutic Use of a Selective S1P(1) Receptor Modulator Ponesimod in Autoimmune Diabetes |
title_short | Therapeutic Use of a Selective S1P(1) Receptor Modulator Ponesimod in Autoimmune Diabetes |
title_sort | therapeutic use of a selective s1p(1) receptor modulator ponesimod in autoimmune diabetes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811978/ https://www.ncbi.nlm.nih.gov/pubmed/24204793 http://dx.doi.org/10.1371/journal.pone.0077296 |
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