Control of intestinal inflammation by glycosylation-dependent lectin-driven immunoregulatory circuits

Diverse immunoregulatory circuits operate to preserve intestinal homeostasis and prevent inflammation. Galectin-1 (Gal1), a β-galactoside-binding protein, promotes homeostasis by reprogramming innate and adaptive immunity. Here, we identify a glycosylation-dependent "on-off" circuit driven...

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Autores principales: Morosi, Luciano Gastón, Cutine, Anabela M., Cagnoni, Alejandro J., Manselle Cocco, Montana N., Merlo, Joaquín P., Morales, Rosa M., May, María, Pérez Sáez, Juan M., Girotti, María Romina, Méndez Huergo, Santiago P., Pucci, Betiana, Gil, Aníbal H., Huernos, Sergio P., Docena, Guillermo Horacio, Sambuelli, Alicia M., Toscano, Marta A., Rabinovich, Gabriel A., Mariño, Karina V.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2021
Materias:
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/124604
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id I19-R120-10915-124604
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Medicina
Ciencias Exactas
intestinal homeostasis
proteins
inflammatory bowel disease (IBD)
spellingShingle Medicina
Ciencias Exactas
intestinal homeostasis
proteins
inflammatory bowel disease (IBD)
Morosi, Luciano Gastón
Cutine, Anabela M.
Cagnoni, Alejandro J.
Manselle Cocco, Montana N.
Merlo, Joaquín P.
Morales, Rosa M.
May, María
Pérez Sáez, Juan M.
Girotti, María Romina
Méndez Huergo, Santiago P.
Pucci, Betiana
Gil, Aníbal H.
Huernos, Sergio P.
Docena, Guillermo Horacio
Sambuelli, Alicia M.
Toscano, Marta A.
Rabinovich, Gabriel A.
Mariño, Karina V.
Control of intestinal inflammation by glycosylation-dependent lectin-driven immunoregulatory circuits
topic_facet Medicina
Ciencias Exactas
intestinal homeostasis
proteins
inflammatory bowel disease (IBD)
description Diverse immunoregulatory circuits operate to preserve intestinal homeostasis and prevent inflammation. Galectin-1 (Gal1), a β-galactoside-binding protein, promotes homeostasis by reprogramming innate and adaptive immunity. Here, we identify a glycosylation-dependent "on-off" circuit driven by Gal1 and its glycosylated ligands that controls intestinal immunopathology by targeting activated CD8⁺ T cells and shaping the cytokine profile. In patients with inflammatory bowel disease (IBD), augmented Gal1 was associated with dysregulated expression of core 2 β6-N-acetylglucosaminyltransferase 1 (C2GNT1) and α(2,6)-sialyltransferase 1 (ST6GAL1), glycosyltransferases responsible for creating or masking Gal1 ligands. Mice lacking Gal1 exhibited exacerbated colitis and augmented mucosal CD8⁺ T cell activation in response to 2,4,6-trinitrobenzenesulfonic acid; this phenotype was partially ameliorated by treatment with recombinant Gal1. While C2gnt1<sup>-/-</sup> mice exhibited aggravated colitis, St6gal1<sup>-/-</sup> mice showed attenuated inflammation. These effects were associated with intrinsic T cell glycosylation. Thus, Gal1 and its glycosylated ligands act to preserve intestinal homeostasis by recalibrating T cell immunity.
format Articulo
Articulo
author Morosi, Luciano Gastón
Cutine, Anabela M.
Cagnoni, Alejandro J.
Manselle Cocco, Montana N.
Merlo, Joaquín P.
Morales, Rosa M.
May, María
Pérez Sáez, Juan M.
Girotti, María Romina
Méndez Huergo, Santiago P.
Pucci, Betiana
Gil, Aníbal H.
Huernos, Sergio P.
Docena, Guillermo Horacio
Sambuelli, Alicia M.
Toscano, Marta A.
Rabinovich, Gabriel A.
Mariño, Karina V.
author_facet Morosi, Luciano Gastón
Cutine, Anabela M.
Cagnoni, Alejandro J.
Manselle Cocco, Montana N.
Merlo, Joaquín P.
Morales, Rosa M.
May, María
Pérez Sáez, Juan M.
Girotti, María Romina
Méndez Huergo, Santiago P.
Pucci, Betiana
Gil, Aníbal H.
Huernos, Sergio P.
Docena, Guillermo Horacio
Sambuelli, Alicia M.
Toscano, Marta A.
Rabinovich, Gabriel A.
Mariño, Karina V.
author_sort Morosi, Luciano Gastón
title Control of intestinal inflammation by glycosylation-dependent lectin-driven immunoregulatory circuits
title_short Control of intestinal inflammation by glycosylation-dependent lectin-driven immunoregulatory circuits
title_full Control of intestinal inflammation by glycosylation-dependent lectin-driven immunoregulatory circuits
title_fullStr Control of intestinal inflammation by glycosylation-dependent lectin-driven immunoregulatory circuits
title_full_unstemmed Control of intestinal inflammation by glycosylation-dependent lectin-driven immunoregulatory circuits
title_sort control of intestinal inflammation by glycosylation-dependent lectin-driven immunoregulatory circuits
publishDate 2021
url http://sedici.unlp.edu.ar/handle/10915/124604
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