Galectin-4 controls intestinal inflammation by selective regulation of peripheral and mucosal T cell apoptosis and cell cycle.
Galectin-4 is a carbohydrate-binding protein belonging to the galectin family. Here we provide novel evidence that galectin-4 is selectively expressed and secreted by intestinal epithelial cells and binds potently to activated peripheral and mucosal lamina propria T-cells at the CD3 epitope. The car...
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2008
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oai:doaj.org-article:d4ec619590404c6ebbd9011ac2f5f0052021-11-25T06:11:41ZGalectin-4 controls intestinal inflammation by selective regulation of peripheral and mucosal T cell apoptosis and cell cycle.1932-620310.1371/journal.pone.0002629https://doaj.org/article/d4ec619590404c6ebbd9011ac2f5f0052008-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18612433/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Galectin-4 is a carbohydrate-binding protein belonging to the galectin family. Here we provide novel evidence that galectin-4 is selectively expressed and secreted by intestinal epithelial cells and binds potently to activated peripheral and mucosal lamina propria T-cells at the CD3 epitope. The carbohydrate-dependent binding of galectin-4 at the CD3 epitope is fully functional and inhibited T cell activation, cycling and expansion. Galectin-4 induced apoptosis of activated peripheral and mucosal lamina propria T cells via calpain-, but not caspase-dependent, pathways. Providing further evidence for its important role in regulating T cell function, galectin-4 blockade by antisense oligonucleotides reduced TNF-alpha inhibitor induced T cell death. Furthermore, in T cells, galectin-4 reduced pro-inflammatory cytokine secretion including IL-17. In a model of experimental colitis, galectin-4 ameliorated mucosal inflammation, induced apoptosis of mucosal T-cells and decreased the secretion of pro-inflammatory cytokines. Our results show that galectin-4 plays a unique role in the intestine and assign a novel role of this protein in controlling intestinal inflammation by a selective induction of T cell apoptosis and cell cycle restriction. Conclusively, after defining its biological role, we propose Galectin-4 is a novel anti-inflammatory agent that could be therapeutically effective in diseases with a disturbed T cell expansion and apoptosis such as inflammatory bowel disease.Daniela PaclikSilvio DaneseUta BerndtBertram WiedenmannAxel DignassAndreas SturmPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 7, p e2629 (2008) |
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Medicine R Science Q Daniela Paclik Silvio Danese Uta Berndt Bertram Wiedenmann Axel Dignass Andreas Sturm Galectin-4 controls intestinal inflammation by selective regulation of peripheral and mucosal T cell apoptosis and cell cycle. |
description |
Galectin-4 is a carbohydrate-binding protein belonging to the galectin family. Here we provide novel evidence that galectin-4 is selectively expressed and secreted by intestinal epithelial cells and binds potently to activated peripheral and mucosal lamina propria T-cells at the CD3 epitope. The carbohydrate-dependent binding of galectin-4 at the CD3 epitope is fully functional and inhibited T cell activation, cycling and expansion. Galectin-4 induced apoptosis of activated peripheral and mucosal lamina propria T cells via calpain-, but not caspase-dependent, pathways. Providing further evidence for its important role in regulating T cell function, galectin-4 blockade by antisense oligonucleotides reduced TNF-alpha inhibitor induced T cell death. Furthermore, in T cells, galectin-4 reduced pro-inflammatory cytokine secretion including IL-17. In a model of experimental colitis, galectin-4 ameliorated mucosal inflammation, induced apoptosis of mucosal T-cells and decreased the secretion of pro-inflammatory cytokines. Our results show that galectin-4 plays a unique role in the intestine and assign a novel role of this protein in controlling intestinal inflammation by a selective induction of T cell apoptosis and cell cycle restriction. Conclusively, after defining its biological role, we propose Galectin-4 is a novel anti-inflammatory agent that could be therapeutically effective in diseases with a disturbed T cell expansion and apoptosis such as inflammatory bowel disease. |
format |
article |
author |
Daniela Paclik Silvio Danese Uta Berndt Bertram Wiedenmann Axel Dignass Andreas Sturm |
author_facet |
Daniela Paclik Silvio Danese Uta Berndt Bertram Wiedenmann Axel Dignass Andreas Sturm |
author_sort |
Daniela Paclik |
title |
Galectin-4 controls intestinal inflammation by selective regulation of peripheral and mucosal T cell apoptosis and cell cycle. |
title_short |
Galectin-4 controls intestinal inflammation by selective regulation of peripheral and mucosal T cell apoptosis and cell cycle. |
title_full |
Galectin-4 controls intestinal inflammation by selective regulation of peripheral and mucosal T cell apoptosis and cell cycle. |
title_fullStr |
Galectin-4 controls intestinal inflammation by selective regulation of peripheral and mucosal T cell apoptosis and cell cycle. |
title_full_unstemmed |
Galectin-4 controls intestinal inflammation by selective regulation of peripheral and mucosal T cell apoptosis and cell cycle. |
title_sort |
galectin-4 controls intestinal inflammation by selective regulation of peripheral and mucosal t cell apoptosis and cell cycle. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2008 |
url |
https://doaj.org/article/d4ec619590404c6ebbd9011ac2f5f005 |
work_keys_str_mv |
AT danielapaclik galectin4controlsintestinalinflammationbyselectiveregulationofperipheralandmucosaltcellapoptosisandcellcycle AT silviodanese galectin4controlsintestinalinflammationbyselectiveregulationofperipheralandmucosaltcellapoptosisandcellcycle AT utaberndt galectin4controlsintestinalinflammationbyselectiveregulationofperipheralandmucosaltcellapoptosisandcellcycle AT bertramwiedenmann galectin4controlsintestinalinflammationbyselectiveregulationofperipheralandmucosaltcellapoptosisandcellcycle AT axeldignass galectin4controlsintestinalinflammationbyselectiveregulationofperipheralandmucosaltcellapoptosisandcellcycle AT andreassturm galectin4controlsintestinalinflammationbyselectiveregulationofperipheralandmucosaltcellapoptosisandcellcycle |
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