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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Autores principales: Daniela Paclik, Silvio Danese, Uta Berndt, Bertram Wiedenmann, Axel Dignass, Andreas Sturm
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Publicado: Public Library of Science (PLoS) 2008
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Acceso en línea:https://doaj.org/article/d4ec619590404c6ebbd9011ac2f5f005
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle 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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