Artículo
Control of intestinal inflammation by glycosylation-dependent lectin-driven immunoregulatory circuits
Morosi, Luciano Gastón
; Cutine, Anabela María
; Cagnoni, Alejandro
; Manselle Cocco, Montana Nicolle
; Croci Russo, Diego Omar
; Merlo, Joaquín Pedro
; Morales, Rosa María
; May, María; Pérez Sáez, Juan Manuel
; Girotti, Maria Romina
; Mendez Huergo, Santiago Patricio
; Pucci, Betiana; Gil, Aníbal H.; Huernos, Sergio P.; Docena, Guillermo H.
; Sambuelli, Alicia; Toscano, Marta Alicia
; Rabinovich, Gabriel Adrián
; Mariño, Karina Valeria
Fecha de publicación:
06/2021
Editorial:
Science Advances is the American Association for the Advancement of Science
Revista:
Science Advances
ISSN:
2375-2548
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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-/- mice exhibited aggravated colitis, St6gal1-/- 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.
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Articulos(IBYME)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Citación
Morosi, Luciano Gastón; Cutine, Anabela María; Cagnoni, Alejandro; Manselle Cocco, Montana Nicolle; Croci Russo, Diego Omar; et al.; Control of intestinal inflammation by glycosylation-dependent lectin-driven immunoregulatory circuits; Science Advances is the American Association for the Advancement of Science; Science Advances; 7; 25; 6-2021
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