Suppression of autoimmune diabetes by soluble galectin-1
Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that targets the β-cells of the pancreas. We investigated the ability of soluble galectin-1 (gal-1), an endogenous lectin that promotes T cell apoptosis, to down-regulate the T cell response that destroys the pancreatic β-cells. We demons...
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todo:paper_00221767_v182_n5_p2641_Perone2023-10-03T14:27:57Z Suppression of autoimmune diabetes by soluble galectin-1 Perone, M.J. Bertera, S. Shufesky, W.J. Divito, S.J. Montecalvo, A. Mathers, A.R. Larregina, A.T. Pang, M. Seth, N. Wucherpfennig, K.W. Trucco, M. Baum, L.G. Morelli, A.E. galectin 1 interleukin 10 interleukin 4 interleukin 5 antidiabetic agent galectin 1 animal cell animal experiment animal model animal tissue article autoimmune disease CD4+ T lymphocyte controlled study diabetes mellitus down regulation helper cell hyperglycemia insulitis mouse nonhuman priority journal regulatory T lymphocyte T lymphocyte animal autoimmune disease Bagg albino mouse female human immunology insulin dependent diabetes mellitus intraperitoneal drug administration metabolism mouse mutant nonobese diabetic mouse pancreas islet beta cell pathology physiology transgenic mouse Animals Autoimmune Diseases Diabetes Mellitus, Type 1 Female Galectin 1 Humans Hypoglycemic Agents Injections, Intraperitoneal Insulin-Secreting Cells Mice Mice, Inbred BALB C Mice, Inbred NOD Mice, SCID Mice, Transgenic Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that targets the β-cells of the pancreas. We investigated the ability of soluble galectin-1 (gal-1), an endogenous lectin that promotes T cell apoptosis, to down-regulate the T cell response that destroys the pancreatic β-cells. We demonstrated that in nonobese diabetic (NOD) mice, gal-1 therapy reduces significantly the amount of Th1 cells, augments the number of T cells secreting IL-4 or IL-10 specific for islet cell Ag, and causes peripheral deletion of β-cell-reactive T cells. Administration of gal-1 prevented the onset of hyperglycemia in NOD mice at early and subclinical stages of T1D. Preventive gal-1 therapy shifted the composition of the insulitis into an infiltrate that did not invade the islets and that contained a significantly reduced number of Th1 cells and a higher percentage of CD4+ T cells with content of IL-4, IL-5, or IL-10. The beneficial effects of gal-1 correlated with the ability of the lectin to trigger apoptosis of the T cell subsets that cause β-cell damage while sparing naive T cells, Th2 lymphocytes, and regulatory T cells in NOD mice. Importantly, gal-1 reversed β-cell autoimmunity and hyperglycemia in NOD mice with ongoing T1D. Because gal-1 therapy did not cause major side effects or β-cell toxicity in NOD mice, the use of gal-1 to control β-cell autoimmunity represents a novel alternative for treatment of subclinical or ongoing T1D. Copyright © 2009 by The American Association of Immunologists, Inc. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00221767_v182_n5_p2641_Perone |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
galectin 1 interleukin 10 interleukin 4 interleukin 5 antidiabetic agent galectin 1 animal cell animal experiment animal model animal tissue article autoimmune disease CD4+ T lymphocyte controlled study diabetes mellitus down regulation helper cell hyperglycemia insulitis mouse nonhuman priority journal regulatory T lymphocyte T lymphocyte animal autoimmune disease Bagg albino mouse female human immunology insulin dependent diabetes mellitus intraperitoneal drug administration metabolism mouse mutant nonobese diabetic mouse pancreas islet beta cell pathology physiology transgenic mouse Animals Autoimmune Diseases Diabetes Mellitus, Type 1 Female Galectin 1 Humans Hypoglycemic Agents Injections, Intraperitoneal Insulin-Secreting Cells Mice Mice, Inbred BALB C Mice, Inbred NOD Mice, SCID Mice, Transgenic |
spellingShingle |
galectin 1 interleukin 10 interleukin 4 interleukin 5 antidiabetic agent galectin 1 animal cell animal experiment animal model animal tissue article autoimmune disease CD4+ T lymphocyte controlled study diabetes mellitus down regulation helper cell hyperglycemia insulitis mouse nonhuman priority journal regulatory T lymphocyte T lymphocyte animal autoimmune disease Bagg albino mouse female human immunology insulin dependent diabetes mellitus intraperitoneal drug administration metabolism mouse mutant nonobese diabetic mouse pancreas islet beta cell pathology physiology transgenic mouse Animals Autoimmune Diseases Diabetes Mellitus, Type 1 Female Galectin 1 Humans Hypoglycemic Agents Injections, Intraperitoneal Insulin-Secreting Cells Mice Mice, Inbred BALB C Mice, Inbred NOD Mice, SCID Mice, Transgenic Perone, M.J. Bertera, S. Shufesky, W.J. Divito, S.J. Montecalvo, A. Mathers, A.R. Larregina, A.T. Pang, M. Seth, N. Wucherpfennig, K.W. Trucco, M. Baum, L.G. Morelli, A.E. Suppression of autoimmune diabetes by soluble galectin-1 |
topic_facet |
galectin 1 interleukin 10 interleukin 4 interleukin 5 antidiabetic agent galectin 1 animal cell animal experiment animal model animal tissue article autoimmune disease CD4+ T lymphocyte controlled study diabetes mellitus down regulation helper cell hyperglycemia insulitis mouse nonhuman priority journal regulatory T lymphocyte T lymphocyte animal autoimmune disease Bagg albino mouse female human immunology insulin dependent diabetes mellitus intraperitoneal drug administration metabolism mouse mutant nonobese diabetic mouse pancreas islet beta cell pathology physiology transgenic mouse Animals Autoimmune Diseases Diabetes Mellitus, Type 1 Female Galectin 1 Humans Hypoglycemic Agents Injections, Intraperitoneal Insulin-Secreting Cells Mice Mice, Inbred BALB C Mice, Inbred NOD Mice, SCID Mice, Transgenic |
description |
Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that targets the β-cells of the pancreas. We investigated the ability of soluble galectin-1 (gal-1), an endogenous lectin that promotes T cell apoptosis, to down-regulate the T cell response that destroys the pancreatic β-cells. We demonstrated that in nonobese diabetic (NOD) mice, gal-1 therapy reduces significantly the amount of Th1 cells, augments the number of T cells secreting IL-4 or IL-10 specific for islet cell Ag, and causes peripheral deletion of β-cell-reactive T cells. Administration of gal-1 prevented the onset of hyperglycemia in NOD mice at early and subclinical stages of T1D. Preventive gal-1 therapy shifted the composition of the insulitis into an infiltrate that did not invade the islets and that contained a significantly reduced number of Th1 cells and a higher percentage of CD4+ T cells with content of IL-4, IL-5, or IL-10. The beneficial effects of gal-1 correlated with the ability of the lectin to trigger apoptosis of the T cell subsets that cause β-cell damage while sparing naive T cells, Th2 lymphocytes, and regulatory T cells in NOD mice. Importantly, gal-1 reversed β-cell autoimmunity and hyperglycemia in NOD mice with ongoing T1D. Because gal-1 therapy did not cause major side effects or β-cell toxicity in NOD mice, the use of gal-1 to control β-cell autoimmunity represents a novel alternative for treatment of subclinical or ongoing T1D. Copyright © 2009 by The American Association of Immunologists, Inc. |
format |
JOUR |
author |
Perone, M.J. Bertera, S. Shufesky, W.J. Divito, S.J. Montecalvo, A. Mathers, A.R. Larregina, A.T. Pang, M. Seth, N. Wucherpfennig, K.W. Trucco, M. Baum, L.G. Morelli, A.E. |
author_facet |
Perone, M.J. Bertera, S. Shufesky, W.J. Divito, S.J. Montecalvo, A. Mathers, A.R. Larregina, A.T. Pang, M. Seth, N. Wucherpfennig, K.W. Trucco, M. Baum, L.G. Morelli, A.E. |
author_sort |
Perone, M.J. |
title |
Suppression of autoimmune diabetes by soluble galectin-1 |
title_short |
Suppression of autoimmune diabetes by soluble galectin-1 |
title_full |
Suppression of autoimmune diabetes by soluble galectin-1 |
title_fullStr |
Suppression of autoimmune diabetes by soluble galectin-1 |
title_full_unstemmed |
Suppression of autoimmune diabetes by soluble galectin-1 |
title_sort |
suppression of autoimmune diabetes by soluble galectin-1 |
url |
http://hdl.handle.net/20.500.12110/paper_00221767_v182_n5_p2641_Perone |
work_keys_str_mv |
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1782027223064117248 |