Dendritic cells expressing transgenic galectin-1 delay onset of autoimmune diabetes in mice

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Type 1 diabetes (T1D) is a disease caused by the destruction of the β cells of the pancreas by activated T cells. Dendritic cells (BC) are the APC that initiate the T cell response that triggers T1D. However, DC also participate in T cell tolerance, and genetic engineering of DC to modulate T cell i...

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Autores principales:	Perone, M.J., Bertera, S., Tawadrous, Z.S., Shufesky, W.J., Piganelli, J.D., Baum, L.G., Trucco, M., Morelli, A.E.
Formato:	Artículo publishedVersion
Lenguaje:	Inglés
Publicado:	2006
Materias:	galectin 1 gamma interferon adoptive transfer animal cell animal experiment animal model animal tissue antigen presenting cell apoptosis article autoimmune disease CD4+ T lymphocyte cellular immunity controlled study cytokine release dendritic cell disease model down regulation female GAL1 gene genetic engineering insulin dependent diabetes mellitus insulitis lymph node lymphocyte proliferation mouse nonhuman pancreas islet beta cell priority journal protein function protein synthesis spleen T lymphocyte activation Th1 cell transgene
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00221767_v177_n8_p5278_Perone
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paperaa:paper_00221767_v177_n8_p5278_Perone
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spelling	paperaa:paper_00221767_v177_n8_p5278_Perone2023-06-12T16:43:57Z Dendritic cells expressing transgenic galectin-1 delay onset of autoimmune diabetes in mice J. Immunol. 2006;177(8):5278-5289 Perone, M.J. Bertera, S. Tawadrous, Z.S. Shufesky, W.J. Piganelli, J.D. Baum, L.G. Trucco, M. Morelli, A.E. galectin 1 gamma interferon adoptive transfer animal cell animal experiment animal model animal tissue antigen presenting cell apoptosis article autoimmune disease CD4+ T lymphocyte cellular immunity controlled study cytokine release dendritic cell disease model down regulation female GAL1 gene genetic engineering insulin dependent diabetes mellitus insulitis lymph node lymphocyte proliferation mouse nonhuman pancreas islet beta cell priority journal protein function protein synthesis spleen T lymphocyte activation Th1 cell transgene Type 1 diabetes (T1D) is a disease caused by the destruction of the β cells of the pancreas by activated T cells. Dendritic cells (BC) are the APC that initiate the T cell response that triggers T1D. However, DC also participate in T cell tolerance, and genetic engineering of DC to modulate T cell immunity is an area of active research. Galectin-1 (gal-1) is an endogenous lectin with regulatory effects on activated T cells including induction of apoptosis and down-regulation of the Th1 response, characteristics that make gal-1 an ideal transgene to transduce DC to treat T1D. We engineered bone marrow-derived DC to synthesize transgenic gal-1 (gal-1-DC) and tested their potential to prevent T1D through their regulatory effects on activated T cells. NOD-derived gal-1-DC triggered rapid apoptosis of diabetogenic BDC2.5 TCR-transgenic CD4+ T cells by TCR-dependent and -independent mechanisms. Intravenously administered gal-1-DC trafficked to pancreatic lymph nodes and spleen and delayed onset of diabetes and insulitis in the NODrag1 -/- lymphocyte adoptive transfer model. The therapeutic effect of gal-1-DC was accompanied by increased percentage of apoptotic T cells and reduced number of IFN-γ-secreting CD4+ T cells in pancreatic lymph nodes. Treatment with gal-1-DC inhibited proliferation and secretion of IFN-γ of T cells in response to β cell Ag. Unlike other DC-based approaches to modulate T cell immunity, the use of the regulatory properties of gal-1-DC on activated T cells might help to delete β cell-reactive T cells at early stages of the disease when the diabetogenic T cells are already activated. Copyright © 2005 by The American Association of Immunologists, Inc. 2006 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00221767_v177_n8_p5278_Perone
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
language	Inglés
orig_language_str_mv	eng
topic	galectin 1 gamma interferon adoptive transfer animal cell animal experiment animal model animal tissue antigen presenting cell apoptosis article autoimmune disease CD4+ T lymphocyte cellular immunity controlled study cytokine release dendritic cell disease model down regulation female GAL1 gene genetic engineering insulin dependent diabetes mellitus insulitis lymph node lymphocyte proliferation mouse nonhuman pancreas islet beta cell priority journal protein function protein synthesis spleen T lymphocyte activation Th1 cell transgene
spellingShingle	galectin 1 gamma interferon adoptive transfer animal cell animal experiment animal model animal tissue antigen presenting cell apoptosis article autoimmune disease CD4+ T lymphocyte cellular immunity controlled study cytokine release dendritic cell disease model down regulation female GAL1 gene genetic engineering insulin dependent diabetes mellitus insulitis lymph node lymphocyte proliferation mouse nonhuman pancreas islet beta cell priority journal protein function protein synthesis spleen T lymphocyte activation Th1 cell transgene Perone, M.J. Bertera, S. Tawadrous, Z.S. Shufesky, W.J. Piganelli, J.D. Baum, L.G. Trucco, M. Morelli, A.E. Dendritic cells expressing transgenic galectin-1 delay onset of autoimmune diabetes in mice
topic_facet	galectin 1 gamma interferon adoptive transfer animal cell animal experiment animal model animal tissue antigen presenting cell apoptosis article autoimmune disease CD4+ T lymphocyte cellular immunity controlled study cytokine release dendritic cell disease model down regulation female GAL1 gene genetic engineering insulin dependent diabetes mellitus insulitis lymph node lymphocyte proliferation mouse nonhuman pancreas islet beta cell priority journal protein function protein synthesis spleen T lymphocyte activation Th1 cell transgene
description	Type 1 diabetes (T1D) is a disease caused by the destruction of the β cells of the pancreas by activated T cells. Dendritic cells (BC) are the APC that initiate the T cell response that triggers T1D. However, DC also participate in T cell tolerance, and genetic engineering of DC to modulate T cell immunity is an area of active research. Galectin-1 (gal-1) is an endogenous lectin with regulatory effects on activated T cells including induction of apoptosis and down-regulation of the Th1 response, characteristics that make gal-1 an ideal transgene to transduce DC to treat T1D. We engineered bone marrow-derived DC to synthesize transgenic gal-1 (gal-1-DC) and tested their potential to prevent T1D through their regulatory effects on activated T cells. NOD-derived gal-1-DC triggered rapid apoptosis of diabetogenic BDC2.5 TCR-transgenic CD4+ T cells by TCR-dependent and -independent mechanisms. Intravenously administered gal-1-DC trafficked to pancreatic lymph nodes and spleen and delayed onset of diabetes and insulitis in the NODrag1 -/- lymphocyte adoptive transfer model. The therapeutic effect of gal-1-DC was accompanied by increased percentage of apoptotic T cells and reduced number of IFN-γ-secreting CD4+ T cells in pancreatic lymph nodes. Treatment with gal-1-DC inhibited proliferation and secretion of IFN-γ of T cells in response to β cell Ag. Unlike other DC-based approaches to modulate T cell immunity, the use of the regulatory properties of gal-1-DC on activated T cells might help to delete β cell-reactive T cells at early stages of the disease when the diabetogenic T cells are already activated. Copyright © 2005 by The American Association of Immunologists, Inc.
format	Artículo Artículo publishedVersion
author	Perone, M.J. Bertera, S. Tawadrous, Z.S. Shufesky, W.J. Piganelli, J.D. Baum, L.G. Trucco, M. Morelli, A.E.
author_facet	Perone, M.J. Bertera, S. Tawadrous, Z.S. Shufesky, W.J. Piganelli, J.D. Baum, L.G. Trucco, M. Morelli, A.E.
author_sort	Perone, M.J.
title	Dendritic cells expressing transgenic galectin-1 delay onset of autoimmune diabetes in mice
title_short	Dendritic cells expressing transgenic galectin-1 delay onset of autoimmune diabetes in mice
title_full	Dendritic cells expressing transgenic galectin-1 delay onset of autoimmune diabetes in mice
title_fullStr	Dendritic cells expressing transgenic galectin-1 delay onset of autoimmune diabetes in mice
title_full_unstemmed	Dendritic cells expressing transgenic galectin-1 delay onset of autoimmune diabetes in mice
title_sort	dendritic cells expressing transgenic galectin-1 delay onset of autoimmune diabetes in mice
publishDate	2006
url	http://hdl.handle.net/20.500.12110/paper_00221767_v177_n8_p5278_Perone
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Dendritic cells expressing transgenic galectin-1 delay onset of autoimmune diabetes in mice

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